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Published in: Acta Neuropathologica 5/2010

Open Access 01-11-2010 | Review

Molecular diagnostics of gliomas: state of the art

Authors: Markus J. Riemenschneider, Judith W. M. Jeuken, Pieter Wesseling, Guido Reifenberger

Published in: Acta Neuropathologica | Issue 5/2010

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Abstract

Modern neuropathology serves a key function in the multidisciplinary management of brain tumor patients. Owing to the recent advancements in molecular neurooncology, the neuropathological assessment of brain tumors is no longer restricted to provide information on a tumor’s histological type and malignancy grade, but may be complemented by a growing number of molecular tests for clinically relevant tissue-based biomarkers. This article provides an overview and critical appraisal of the types of genetic and epigenetic aberrations that have gained significance in the molecular diagnostics of gliomas, namely deletions of chromosome arms 1p and 19q, promoter hypermethylation of the O6-methylguanine-methyl-transferase (MGMT) gene, and the mutation status of the IDH1 and IDH2 genes. In addition, the frequent oncogenic aberration of BRAF in pilocytic astrocytomas may serve as a novel diagnostic marker and therapeutic target. Finally, this review will summarize recent mechanistic insights into the molecular alterations underlying treatment resistance in malignant gliomas and outline the potential of genome-wide profiling approaches for increasing our repertoire of clinically useful glioma markers.
Literature
1.
go back to reference Antonelli M, Buttarelli FR, Arcella A, Nobusawa S, Donofrio V, Oghaki H and Giangaspero F (2010) Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high-grade gliomas. J Neurooncol [Epub ahead of print] Antonelli M, Buttarelli FR, Arcella A, Nobusawa S, Donofrio V, Oghaki H and Giangaspero F (2010) Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high-grade gliomas. J Neurooncol [Epub ahead of print]
2.
go back to reference Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116:597–602PubMedCrossRef Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116:597–602PubMedCrossRef
3.
go back to reference Bar EE, Lin A, Tihan T, Burger PC, Eberhart CG (2008) Frequent gains at chromosome 7q34 involving BRAF in pilocytic astrocytoma. J Neuropathol Exp Neurol 67:878–887PubMedCrossRef Bar EE, Lin A, Tihan T, Burger PC, Eberhart CG (2008) Frequent gains at chromosome 7q34 involving BRAF in pilocytic astrocytoma. J Neuropathol Exp Neurol 67:878–887PubMedCrossRef
4.
go back to reference Barker FG 2nd, Simmons ML, Chang SM, Prados MD, Larson DA, Sneed PK, Wara WM, Berger MS, Chen P, Israel MA, Aldape KD (2001) EGFR overexpression and radiation response in glioblastoma multiforme. Int J Radiat Oncol Biol Phys 51:410–418PubMed Barker FG 2nd, Simmons ML, Chang SM, Prados MD, Larson DA, Sneed PK, Wara WM, Berger MS, Chen P, Israel MA, Aldape KD (2001) EGFR overexpression and radiation response in glioblastoma multiforme. Int J Radiat Oncol Biol Phys 51:410–418PubMed
5.
go back to reference Bayley JP, Devilee P (2010) Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree? Curr Opin Genet Dev 20:324–329PubMedCrossRef Bayley JP, Devilee P (2010) Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree? Curr Opin Genet Dev 20:324–329PubMedCrossRef
6.
go back to reference Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ, Aigner L, Brawanski A, Bogdahn U, Beier CP (2007) CD133(+) and CD133(−) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 67:4010–4015PubMedCrossRef Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ, Aigner L, Brawanski A, Bogdahn U, Beier CP (2007) CD133(+) and CD133(−) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 67:4010–4015PubMedCrossRef
7.
go back to reference Belanich M, Pastor M, Randall T, Guerra D, Kibitel J, Alas L, Li B, Citron M, Wasserman P, White A, Eyre H, Jaeckle K, Schulman S, Rector D, Prados M, Coons S, Shapiro W, Yarosh D (1996) Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res 56:783–788PubMed Belanich M, Pastor M, Randall T, Guerra D, Kibitel J, Alas L, Li B, Citron M, Wasserman P, White A, Eyre H, Jaeckle K, Schulman S, Rector D, Prados M, Coons S, Shapiro W, Yarosh D (1996) Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res 56:783–788PubMed
8.
go back to reference Bleeker FE, Lamba S, Leenstra S, Troost D, Hulsebos T, Vandertop WP, Frattini M, Molinari F, Knowles M, Cerrato A, Rodolfo M, Scarpa A, Felicioni L, Buttitta F, Malatesta S, Marchetti A, Bardelli A (2009) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30:7–11PubMedCrossRef Bleeker FE, Lamba S, Leenstra S, Troost D, Hulsebos T, Vandertop WP, Frattini M, Molinari F, Knowles M, Cerrato A, Rodolfo M, Scarpa A, Felicioni L, Buttitta F, Malatesta S, Marchetti A, Bardelli A (2009) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30:7–11PubMedCrossRef
9.
go back to reference Brandes AA, Nicolardi L, Tosoni A, Gardiman M, Iuzzolino P, Ghimenton C, Reni M, Rotilio A, Sotti G, Ermani M (2006) Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma. Neuro Oncol 8:253–260PubMedCrossRef Brandes AA, Nicolardi L, Tosoni A, Gardiman M, Iuzzolino P, Ghimenton C, Reni M, Rotilio A, Sotti G, Ermani M (2006) Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma. Neuro Oncol 8:253–260PubMedCrossRef
10.
go back to reference Brat DJ, Castellano-Sanchez AA, Hunter SB, Pecot M, Cohen C, Hammond EH, Devi SN, Kaur B, Van Meir EG (2004) Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population. Cancer Res 64:920–927PubMedCrossRef Brat DJ, Castellano-Sanchez AA, Hunter SB, Pecot M, Cohen C, Hammond EH, Devi SN, Kaur B, Van Meir EG (2004) Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population. Cancer Res 64:920–927PubMedCrossRef
11.
go back to reference Brat DJ, Van Meir EG (2004) Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma. Lab Invest 84:397–405PubMedCrossRef Brat DJ, Van Meir EG (2004) Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma. Lab Invest 84:397–405PubMedCrossRef
12.
go back to reference Brokinkel B, Fischer BR, Peetz-Dienhart S, Ebel H, Sepehrnia A, Rama B, Albert FK, Stummer W, Paulus W and Hasselblatt M (2010) MGMT promoter methylation status in anaplastic meningiomas. J Neurooncol [Epub ahead of print] Brokinkel B, Fischer BR, Peetz-Dienhart S, Ebel H, Sepehrnia A, Rama B, Albert FK, Stummer W, Paulus W and Hasselblatt M (2010) MGMT promoter methylation status in anaplastic meningiomas. J Neurooncol [Epub ahead of print]
13.
go back to reference Buccoliero AM, Castiglione F, Rossi Degl’Innocenti D, Paglierani M, Maio V, Gheri CF, Garbini F, Moncini D, Taddei A, Sardi I, Sanzo M, Giordano F, Mussa F, Genitori L, Taddei GL (2008) O6-Methylguanine-DNA-methyltransferase in recurring anaplastic ependymomas: PCR and immunohistochemistry. J Chemother 20:263–268PubMed Buccoliero AM, Castiglione F, Rossi Degl’Innocenti D, Paglierani M, Maio V, Gheri CF, Garbini F, Moncini D, Taddei A, Sardi I, Sanzo M, Giordano F, Mussa F, Genitori L, Taddei GL (2008) O6-Methylguanine-DNA-methyltransferase in recurring anaplastic ependymomas: PCR and immunohistochemistry. J Chemother 20:263–268PubMed
14.
go back to reference Bujko M, Kober P, Matyja E, Nauman P, Dyttus-Cebulok K, Czeremszynska B, Bonicki W, Siedlecki JA (2010) Prognostic value of IDH1 mutations identified with PCR-RFLP assay in glioblastoma patients. Mol Diagn Ther 14:163–169PubMed Bujko M, Kober P, Matyja E, Nauman P, Dyttus-Cebulok K, Czeremszynska B, Bonicki W, Siedlecki JA (2010) Prognostic value of IDH1 mutations identified with PCR-RFLP assay in glioblastoma patients. Mol Diagn Ther 14:163–169PubMed
15.
go back to reference Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, Batchelor TT, Futreal PA, Stratton MR, Curry WT, Iafrate AJ, Louis DN (2007) Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res 13:2038–2045PubMedCrossRef Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, Batchelor TT, Futreal PA, Stratton MR, Curry WT, Iafrate AJ, Louis DN (2007) Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res 13:2038–2045PubMedCrossRef
16.
go back to reference Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W (2006) Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 24:2707–2714PubMedCrossRef Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W (2006) Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 24:2707–2714PubMedCrossRef
17.
go back to reference Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479PubMedCrossRef Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479PubMedCrossRef
18.
go back to reference Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068CrossRef Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068CrossRef
19.
go back to reference Capper D, Weissert S, Balss J, Habel A, Meyer J, Jager D, Ackermann U, Tessmer C, Korshunov A, Zentgraf H, Hartmann C, von Deimling A (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254PubMedCrossRef Capper D, Weissert S, Balss J, Habel A, Meyer J, Jager D, Ackermann U, Tessmer C, Korshunov A, Zentgraf H, Hartmann C, von Deimling A (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254PubMedCrossRef
20.
go back to reference Chakravarti A, Chakladar A, Delaney MA, Latham DE, Loeffler JS (2002) The epidermal growth factor receptor pathway mediates resistance to sequential administration of radiation and chemotherapy in primary human glioblastoma cells in a RAS-dependent manner. Cancer Res 62:4307–4315PubMed Chakravarti A, Chakladar A, Delaney MA, Latham DE, Loeffler JS (2002) The epidermal growth factor receptor pathway mediates resistance to sequential administration of radiation and chemotherapy in primary human glioblastoma cells in a RAS-dependent manner. Cancer Res 62:4307–4315PubMed
21.
go back to reference Cheng CL, Johnson SP, Keir ST, Quinn JA, Ali-Osman F, Szabo C, Li H, Salzman AL, Dolan ME, Modrich P, Bigner DD, Friedman HS (2005) Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft. Mol Cancer Ther 4:1364–1368PubMedCrossRef Cheng CL, Johnson SP, Keir ST, Quinn JA, Ali-Osman F, Szabo C, Li H, Salzman AL, Dolan ME, Modrich P, Bigner DD, Friedman HS (2005) Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft. Mol Cancer Ther 4:1364–1368PubMedCrossRef
22.
go back to reference Chinot OL, Barrie M, Fuentes S, Eudes N, Lancelot S, Metellus P, Muracciole X, Braguer D, Ouafik L, Martin PM, Dufour H, Figarella-Branger D (2007) Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol 25:1470–1475PubMedCrossRef Chinot OL, Barrie M, Fuentes S, Eudes N, Lancelot S, Metellus P, Muracciole X, Braguer D, Ouafik L, Martin PM, Dufour H, Figarella-Branger D (2007) Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol 25:1470–1475PubMedCrossRef
23.
go back to reference Chou WC, Hou HA, Chen CY, Tang JL, Yao M, Tsay W, Ko BS, Wu SJ, Huang SY, Hsu SC, Chen YC, Huang YN, Chang YC, Lee FY, Liu MC, Liu CW, Tseng MH, Huang CF, Tien HF (2010) Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation. Blood 115:2749–2754PubMedCrossRef Chou WC, Hou HA, Chen CY, Tang JL, Yao M, Tsay W, Ko BS, Wu SJ, Huang SY, Hsu SC, Chen YC, Huang YN, Chang YC, Lee FY, Liu MC, Liu CW, Tseng MH, Huang CF, Tien HF (2010) Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation. Blood 115:2749–2754PubMedCrossRef
24.
go back to reference Claes A, Idema AJ, Wesseling P (2007) Diffuse glioma growth: a guerilla war. Acta Neuropathol 114:443–458PubMedCrossRef Claes A, Idema AJ, Wesseling P (2007) Diffuse glioma growth: a guerilla war. Acta Neuropathol 114:443–458PubMedCrossRef
25.
go back to reference Colman H, Zhang L, Sulman EP, McDonald JM, Shooshtari NL, Rivera A, Popoff S, Nutt CL, Louis DN, Cairncross JG, Gilbert MR, Phillips HS, Mehta MP, Chakravarti A, Pelloski CE, Bhat K, Feuerstein BG, Jenkins RB, Aldape K (2010) A multigene predictor of outcome in glioblastoma. Neuro Oncol 12:49–57PubMed Colman H, Zhang L, Sulman EP, McDonald JM, Shooshtari NL, Rivera A, Popoff S, Nutt CL, Louis DN, Cairncross JG, Gilbert MR, Phillips HS, Mehta MP, Chakravarti A, Pelloski CE, Bhat K, Feuerstein BG, Jenkins RB, Aldape K (2010) A multigene predictor of outcome in glioblastoma. Neuro Oncol 12:49–57PubMed
26.
go back to reference Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744PubMedCrossRef Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744PubMedCrossRef
27.
go back to reference Dehais C, Laigle-Donadey F, Marie Y, Kujas M, Lejeune J, Benouaich-Amiel A, Pedretti M, Polivka M, Xuan KH, Thillet J, Delattre JY, Sanson M (2006) Prognostic stratification of patients with anaplastic gliomas according to genetic profile. Cancer 107:1891–1897PubMedCrossRef Dehais C, Laigle-Donadey F, Marie Y, Kujas M, Lejeune J, Benouaich-Amiel A, Pedretti M, Polivka M, Xuan KH, Thillet J, Delattre JY, Sanson M (2006) Prognostic stratification of patients with anaplastic gliomas according to genetic profile. Cancer 107:1891–1897PubMedCrossRef
28.
go back to reference Delic S, Schmidt N, Lottmann N, Stefanski A, Stuhler K, Reifenberger G, Riemenschneider MJ (2009) In vivo and in vitro selection of infiltrating glioma cells: a comprehensive, multi-dimensional molecular analysis of the invasive phenotype of human glioblastomas. Acta Neuropathol 118:437–437 (Meeting Abstract) Delic S, Schmidt N, Lottmann N, Stefanski A, Stuhler K, Reifenberger G, Riemenschneider MJ (2009) In vivo and in vitro selection of infiltrating glioma cells: a comprehensive, multi-dimensional molecular analysis of the invasive phenotype of human glioblastomas. Acta Neuropathol 118:437–437 (Meeting Abstract)
29.
go back to reference Dong S, Nutt CL, Betensky RA, Stemmer-Rachamimov AO, Denko NC, Ligon KL, Rowitch DH, Louis DN (2005) Histology-based expression profiling yields novel prognostic markers in human glioblastoma. J Neuropathol Exp Neurol 64:948–955PubMedCrossRef Dong S, Nutt CL, Betensky RA, Stemmer-Rachamimov AO, Denko NC, Ligon KL, Rowitch DH, Louis DN (2005) Histology-based expression profiling yields novel prognostic markers in human glioblastoma. J Neuropathol Exp Neurol 64:948–955PubMedCrossRef
30.
go back to reference Dubbink HJ, Taal W, van Marion R, Kros JM, van Heuvel I, Bromberg JE, Zonnenberg BA, Zonnenberg CB, Postma TJ, Gijtenbeek JM, Boogerd W, Groenendijk FH, Smitt PA, Dinjens WN, van den Bent MJ (2009) IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide. Neurology 73:1792–1795PubMedCrossRef Dubbink HJ, Taal W, van Marion R, Kros JM, van Heuvel I, Bromberg JE, Zonnenberg BA, Zonnenberg CB, Postma TJ, Gijtenbeek JM, Boogerd W, Groenendijk FH, Smitt PA, Dinjens WN, van den Bent MJ (2009) IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide. Neurology 73:1792–1795PubMedCrossRef
31.
go back to reference Ebinger M, Senf L, Wachowski O, Scheurlen W (2004) Promoter methylation pattern of caspase-8, P16INK4A, MGMT, TIMP-3, and E-cadherin in medulloblastoma. Pathol Oncol Res 10:17–21PubMedCrossRef Ebinger M, Senf L, Wachowski O, Scheurlen W (2004) Promoter methylation pattern of caspase-8, P16INK4A, MGMT, TIMP-3, and E-cadherin in medulloblastoma. Pathol Oncol Res 10:17–21PubMedCrossRef
32.
go back to reference Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354PubMedCrossRef Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354PubMedCrossRef
33.
go back to reference Felsberg J, Erkwoh A, Sabel MC, Kirsch L, Fimmers R, Blaschke B, Schlegel U, Schramm J, Wiestler OD, Reifenberger G (2004) Oligodendroglial tumors: refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival. Brain Pathol 14:121–130PubMedCrossRef Felsberg J, Erkwoh A, Sabel MC, Kirsch L, Fimmers R, Blaschke B, Schlegel U, Schramm J, Wiestler OD, Reifenberger G (2004) Oligodendroglial tumors: refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival. Brain Pathol 14:121–130PubMedCrossRef
34.
go back to reference Felsberg J, Rapp M, Loeser S, Fimmers R, Stummer W, Goeppert M, Steiger HJ, Friedensdorf B, Reifenberger G, Sabel MC (2009) Prognostic significance of molecular markers and extent of resection in primary glioblastoma patients. Clin Cancer Res 15:6683–6693PubMedCrossRef Felsberg J, Rapp M, Loeser S, Fimmers R, Stummer W, Goeppert M, Steiger HJ, Friedensdorf B, Reifenberger G, Sabel MC (2009) Prognostic significance of molecular markers and extent of resection in primary glioblastoma patients. Clin Cancer Res 15:6683–6693PubMedCrossRef
35.
go back to reference Felsberg J, Wolter M, Seul H, Friedensdorf B, Goppert M, Sabel MC, Reifenberger G (2010) Rapid and sensitive assessment of the IDH1 and IDH2 mutation status in cerebral gliomas based on DNA pyrosequencing. Acta Neuropathol 119:501–507PubMedCrossRef Felsberg J, Wolter M, Seul H, Friedensdorf B, Goppert M, Sabel MC, Reifenberger G (2010) Rapid and sensitive assessment of the IDH1 and IDH2 mutation status in cerebral gliomas based on DNA pyrosequencing. Acta Neuropathol 119:501–507PubMedCrossRef
36.
go back to reference Fu Y, Huang R, Du J, Yang R, An N, Liang A (2010) Glioma-derived mutations in IDH: from mechanism to potential therapy. Biochem Biophys Res Commun 397:127–130PubMedCrossRef Fu Y, Huang R, Du J, Yang R, An N, Liang A (2010) Glioma-derived mutations in IDH: from mechanism to potential therapy. Biochem Biophys Res Commun 397:127–130PubMedCrossRef
37.
go back to reference Gaal J, Burnichon N, Korpershoek E, Roncelin I, Bertherat J, Plouin PF, de Krijger RR, Gimenez-Roqueplo AP, Dinjens WN (2010) Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 95:1274–1278PubMedCrossRef Gaal J, Burnichon N, Korpershoek E, Roncelin I, Bertherat J, Plouin PF, de Krijger RR, Gimenez-Roqueplo AP, Dinjens WN (2010) Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 95:1274–1278PubMedCrossRef
38.
go back to reference Gan HK, Kaye AH, Luwor RB (2009) The EGFRvIII variant in glioblastoma multiforme. J Clin Neurosci 16:748–754PubMedCrossRef Gan HK, Kaye AH, Luwor RB (2009) The EGFRvIII variant in glioblastoma multiforme. J Clin Neurosci 16:748–754PubMedCrossRef
39.
go back to reference Gerson SL (2004) MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 4:296–307PubMedCrossRef Gerson SL (2004) MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 4:296–307PubMedCrossRef
40.
go back to reference Giannini C, Burger PC, Berkey BA, Cairncross JG, Jenkins RB, Mehta M, Curran WJ, Aldape K (2008) Anaplastic oligodendroglial tumors: refining the correlation among histopathology, 1p 19q deletion and clinical outcome in Intergroup Radiation Therapy Oncology Group Trial 9402. Brain Pathol 18:360–369PubMedCrossRef Giannini C, Burger PC, Berkey BA, Cairncross JG, Jenkins RB, Mehta M, Curran WJ, Aldape K (2008) Anaplastic oligodendroglial tumors: refining the correlation among histopathology, 1p 19q deletion and clinical outcome in Intergroup Radiation Therapy Oncology Group Trial 9402. Brain Pathol 18:360–369PubMedCrossRef
41.
go back to reference Gravendeel LA, Kloosterhof NK, Bralten LB, van Marion R, Dubbink HJ, Dinjens W, Bleeker FE, Hoogenraad CC, Michiels E, Kros JM, van den Bent M, Smitt PA, French PJ (2010) Segregation of non-p.R132H mutations in IDH1 in distinct molecular subtypes of glioma. Hum Mutat 31:E1186–E1199PubMedCrossRef Gravendeel LA, Kloosterhof NK, Bralten LB, van Marion R, Dubbink HJ, Dinjens W, Bleeker FE, Hoogenraad CC, Michiels E, Kros JM, van den Bent M, Smitt PA, French PJ (2010) Segregation of non-p.R132H mutations in IDH1 in distinct molecular subtypes of glioma. Hum Mutat 31:E1186–E1199PubMedCrossRef
42.
go back to reference Griffin CA, Burger P, Morsberger L, Yonescu R, Swierczynski S, Weingart JD, Murphy KM (2006) Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss. J Neuropathol Exp Neurol 65:988–994PubMedCrossRef Griffin CA, Burger P, Morsberger L, Yonescu R, Swierczynski S, Weingart JD, Murphy KM (2006) Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss. J Neuropathol Exp Neurol 65:988–994PubMedCrossRef
43.
go back to reference Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG, Sasaki M, Jin S, Schenkein DP, Su SM, Dang L, Fantin VR, Mak TW (2010) Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 207:339–344PubMedCrossRef Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG, Sasaki M, Jin S, Schenkein DP, Su SM, Dang L, Fantin VR, Mak TW (2010) Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 207:339–344PubMedCrossRef
44.
go back to reference Haas-Kogan DA, Prados MD, Tihan T, Eberhard DA, Jelluma N, Arvold ND, Baumber R, Lamborn KR, Kapadia A, Malec M, Berger MS, Stokoe D (2005) Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib. J Natl Cancer Inst 97:880–887PubMedCrossRef Haas-Kogan DA, Prados MD, Tihan T, Eberhard DA, Jelluma N, Arvold ND, Baumber R, Lamborn KR, Kapadia A, Malec M, Berger MS, Stokoe D (2005) Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib. J Natl Cancer Inst 97:880–887PubMedCrossRef
45.
go back to reference Halatsch ME, Schmidt U, Behnke-Mursch J, Unterberg A, Wirtz CR (2006) Epidermal growth factor receptor inhibition for the treatment of glioblastoma multiforme and other malignant brain tumours. Cancer Treat Rev 32:74–89PubMedCrossRef Halatsch ME, Schmidt U, Behnke-Mursch J, Unterberg A, Wirtz CR (2006) Epidermal growth factor receptor inhibition for the treatment of glioblastoma multiforme and other malignant brain tumours. Cancer Treat Rev 32:74–89PubMedCrossRef
46.
go back to reference Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, Felsberg J, Wolter M, Mawrin C, Wick W, Weller M, Herold-Mende C, Unterberg A, Jeuken JW, Wesseling P, Reifenberger G, von Deimling A (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118:469–474PubMedCrossRef Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, Felsberg J, Wolter M, Mawrin C, Wick W, Weller M, Herold-Mende C, Unterberg A, Jeuken JW, Wesseling P, Reifenberger G, von Deimling A (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118:469–474PubMedCrossRef
47.
go back to reference Hatanpaa KJ, Burger PC, Eshleman JR, Murphy KM, Berg KD (2003) Molecular diagnosis of oligodendroglioma in paraffin sections. Lab Invest 83:419–428PubMed Hatanpaa KJ, Burger PC, Eshleman JR, Murphy KM, Berg KD (2003) Molecular diagnosis of oligodendroglioma in paraffin sections. Lab Invest 83:419–428PubMed
48.
go back to reference Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRef Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRef
49.
go back to reference Heimberger AB, Crotty LE, Archer GE, Hess KR, Wikstrand CJ, Friedman AH, Friedman HS, Bigner DD, Sampson JH (2003) Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res 9:4247–4254PubMed Heimberger AB, Crotty LE, Archer GE, Hess KR, Wikstrand CJ, Friedman AH, Friedman HS, Bigner DD, Sampson JH (2003) Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res 9:4247–4254PubMed
50.
go back to reference Heimberger AB, Hlatky R, Suki D, Yang D, Weinberg J, Gilbert M, Sawaya R, Aldape K (2005) Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res 11:1462–1466PubMedCrossRef Heimberger AB, Hlatky R, Suki D, Yang D, Weinberg J, Gilbert M, Sawaya R, Aldape K (2005) Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res 11:1462–1466PubMedCrossRef
51.
go back to reference Heimberger AB, Sampson JH (2009) The PEPvIII-KLH (CDX-110) vaccine in glioblastoma multiforme patients. Expert Opin Biol Ther 9:1087–1098PubMedCrossRef Heimberger AB, Sampson JH (2009) The PEPvIII-KLH (CDX-110) vaccine in glioblastoma multiforme patients. Expert Opin Biol Ther 9:1087–1098PubMedCrossRef
52.
go back to reference Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 93:9821–9826PubMedCrossRef Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 93:9821–9826PubMedCrossRef
53.
go back to reference Herrlinger U, Rieger J, Koch D, Loeser S, Blaschke B, Kortmann RD, Steinbach JP, Hundsberger T, Wick W, Meyermann R, Tan TC, Sommer C, Bamberg M, Reifenberger G, Weller M (2006) Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. J Clin Oncol 24:4412–4417PubMedCrossRef Herrlinger U, Rieger J, Koch D, Loeser S, Blaschke B, Kortmann RD, Steinbach JP, Hundsberger T, Wick W, Meyermann R, Tan TC, Sommer C, Bamberg M, Reifenberger G, Weller M (2006) Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. J Clin Oncol 24:4412–4417PubMedCrossRef
54.
go back to reference Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ, McDonough WS, Sloan A, Coons SW, Berens ME (2005) Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia 7:7–16PubMedCrossRef Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ, McDonough WS, Sloan A, Coons SW, Berens ME (2005) Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia 7:7–16PubMedCrossRef
55.
go back to reference Horbinski C, Kelly L, Nikiforov YE, Durso MB, Nikiforova MN (2010) Detection of IDH1 and IDH2 mutations by fluorescence melting curve analysis as a diagnostic tool for brain biopsies. J Mol Diagn 12:487–492PubMedCrossRef Horbinski C, Kelly L, Nikiforov YE, Durso MB, Nikiforova MN (2010) Detection of IDH1 and IDH2 mutations by fluorescence melting curve analysis as a diagnostic tool for brain biopsies. J Mol Diagn 12:487–492PubMedCrossRef
56.
go back to reference Horbinski C, Kofler J, Kelly LM, Murdoch GH, Nikiforova MN (2009) Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. J Neuropathol Exp Neurol 68:1319–1325PubMedCrossRef Horbinski C, Kofler J, Kelly LM, Murdoch GH, Nikiforova MN (2009) Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. J Neuropathol Exp Neurol 68:1319–1325PubMedCrossRef
57.
go back to reference Hunter C, Smith R, Cahill DP, Stephens P, Stevens C, Teague J, Greenman C, Edkins S, Bignell G, Davies H, O’Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Butler A, Clements J, Cole J, Dicks E, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Richardson D, Shepherd R, Small A, Solomon H, Tofts C, Varian J, West S, Widaa S, Yates A, Easton DF, Riggins G, Roy JE, Levine KK, Mueller W, Batchelor TT, Louis DN, Stratton MR, Futreal PA, Wooster R (2006) A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res 66:3987–3991PubMedCrossRef Hunter C, Smith R, Cahill DP, Stephens P, Stevens C, Teague J, Greenman C, Edkins S, Bignell G, Davies H, O’Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Butler A, Clements J, Cole J, Dicks E, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Richardson D, Shepherd R, Small A, Solomon H, Tofts C, Varian J, West S, Widaa S, Yates A, Easton DF, Riggins G, Roy JE, Levine KK, Mueller W, Batchelor TT, Louis DN, Stratton MR, Futreal PA, Wooster R (2006) A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res 66:3987–3991PubMedCrossRef
58.
go back to reference Ichimura K, Pearson DM, Kocialkowski S, Backlund LM, Chan R, Jones DT, Collins VP (2009) IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro Oncol 11:341–347PubMedCrossRef Ichimura K, Pearson DM, Kocialkowski S, Backlund LM, Chan R, Jones DT, Collins VP (2009) IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro Oncol 11:341–347PubMedCrossRef
59.
go back to reference Ino Y, Betensky RA, Zlatescu MC, Sasaki H, Macdonald DR, Stemmer-Rachamimov AO, Ramsay DA, Cairncross JG, Louis DN (2001) Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. Clin Cancer Res 7:839–845PubMed Ino Y, Betensky RA, Zlatescu MC, Sasaki H, Macdonald DR, Stemmer-Rachamimov AO, Ramsay DA, Cairncross JG, Louis DN (2001) Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. Clin Cancer Res 7:839–845PubMed
60.
go back to reference International Cancer Genome Consortium (2010) International network of cancer genome projects. Nature 464:993–998CrossRef International Cancer Genome Consortium (2010) International network of cancer genome projects. Nature 464:993–998CrossRef
61.
go back to reference Jaeckle KA, Eyre HJ, Townsend JJ, Schulman S, Knudson HM, Belanich M, Yarosh DB, Bearman SI, Giroux DJ, Schold SC (1998) Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study. J Clin Oncol 16:3310–3315PubMed Jaeckle KA, Eyre HJ, Townsend JJ, Schulman S, Knudson HM, Belanich M, Yarosh DB, Bearman SI, Giroux DJ, Schold SC (1998) Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study. J Clin Oncol 16:3310–3315PubMed
62.
go back to reference Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M, Flynn H, Passe S, Felten S, Brown PD, Shaw EG, Buckner JC (2006) A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 66:9852–9861PubMedCrossRef Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M, Flynn H, Passe S, Felten S, Brown PD, Shaw EG, Buckner JC (2006) A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 66:9852–9861PubMedCrossRef
63.
go back to reference Jeuken J, Cornelissen S, Boots-Sprenger S, Gijsen S, Wesseling P (2006) Multiplex ligation-dependent probe amplification: a diagnostic tool for simultaneous identification of different genetic markers in glial tumors. J Mol Diagn 8:433–443PubMedCrossRef Jeuken J, Cornelissen S, Boots-Sprenger S, Gijsen S, Wesseling P (2006) Multiplex ligation-dependent probe amplification: a diagnostic tool for simultaneous identification of different genetic markers in glial tumors. J Mol Diagn 8:433–443PubMedCrossRef
64.
go back to reference Jeuken J, Sijben A, Alenda C, Rijntjes J, Dekkers M, Boots-Sprenger S, McLendon R, Wesseling P (2009) Robust detection of EGFR copy number changes and EGFR variant III: technical aspects and relevance for glioma diagnostics. Brain Pathol 19:661–671PubMedCrossRef Jeuken J, Sijben A, Alenda C, Rijntjes J, Dekkers M, Boots-Sprenger S, McLendon R, Wesseling P (2009) Robust detection of EGFR copy number changes and EGFR variant III: technical aspects and relevance for glioma diagnostics. Brain Pathol 19:661–671PubMedCrossRef
65.
go back to reference Jeuken JW, Cornelissen SJ, Vriezen M, Dekkers MM, Errami A, Sijben A, Boots-Sprenger SH, Wesseling P (2007) MS-MLPA: an attractive alternative laboratory assay for robust, reliable, and semiquantitative detection of MGMT promoter hypermethylation in gliomas. Lab Invest 87:1055–1065PubMedCrossRef Jeuken JW, Cornelissen SJ, Vriezen M, Dekkers MM, Errami A, Sijben A, Boots-Sprenger SH, Wesseling P (2007) MS-MLPA: an attractive alternative laboratory assay for robust, reliable, and semiquantitative detection of MGMT promoter hypermethylation in gliomas. Lab Invest 87:1055–1065PubMedCrossRef
66.
go back to reference Jeuken JW, Sprenger SH, Boerman RH, von Deimling A, Teepen HL, van Overbeeke JJ, Wesseling P (2001) Subtyping of oligo-astrocytic tumours by comparative genomic hybridization. J Pathol 194:81–87PubMedCrossRef Jeuken JW, Sprenger SH, Boerman RH, von Deimling A, Teepen HL, van Overbeeke JJ, Wesseling P (2001) Subtyping of oligo-astrocytic tumours by comparative genomic hybridization. J Pathol 194:81–87PubMedCrossRef
67.
go back to reference Jeuken JW, Sprenger SH, Wesseling P, Macville MV, von Deimling A, Teepen HL, van Overbeeke JJ, Boerman RH (1999) Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization. J Neuropathol Exp Neurol 58:606–612PubMedCrossRef Jeuken JW, Sprenger SH, Wesseling P, Macville MV, von Deimling A, Teepen HL, van Overbeeke JJ, Boerman RH (1999) Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization. J Neuropathol Exp Neurol 58:606–612PubMedCrossRef
68.
go back to reference Jeuken JW, von Deimling A, Wesseling P (2004) Molecular pathogenesis of oligodendroglial tumors. J Neurooncol 70:161–181PubMedCrossRef Jeuken JW, von Deimling A, Wesseling P (2004) Molecular pathogenesis of oligodendroglial tumors. J Neurooncol 70:161–181PubMedCrossRef
69.
go back to reference Jones DT, Kocialkowski S, Liu L, Pearson DM, Backlund LM, Ichimura K, Collins VP (2008) Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 68:8673–8677PubMedCrossRef Jones DT, Kocialkowski S, Liu L, Pearson DM, Backlund LM, Ichimura K, Collins VP (2008) Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 68:8673–8677PubMedCrossRef
70.
go back to reference Jones DT, Kocialkowski S, Liu L, Pearson DM, Ichimura K, Collins VP (2009) Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549:BRAF fusion in activating the MAPK pathway in pilocytic astrocytoma. Oncogene 28:2119–2123PubMedCrossRef Jones DT, Kocialkowski S, Liu L, Pearson DM, Ichimura K, Collins VP (2009) Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549:BRAF fusion in activating the MAPK pathway in pilocytic astrocytoma. Oncogene 28:2119–2123PubMedCrossRef
71.
go back to reference Kang MR, Kim MS, Oh JE, Kim YR, Song SY, Seo SI, Lee JY, Yoo NJ, Lee SH (2009) Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Cancer 125:353–355PubMedCrossRef Kang MR, Kim MS, Oh JE, Kim YR, Song SY, Seo SI, Lee JY, Yoo NJ, Lee SH (2009) Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Cancer 125:353–355PubMedCrossRef
72.
go back to reference Kato Y, Jin G, Kuan CT, McLendon RE, Yan H, Bigner DD (2009) A monoclonal antibody IMab-1 specifically recognizes IDH1R132H, the most common glioma-derived mutation. Biochem Biophys Res Commun 390:547–551PubMedCrossRef Kato Y, Jin G, Kuan CT, McLendon RE, Yan H, Bigner DD (2009) A monoclonal antibody IMab-1 specifically recognizes IDH1R132H, the most common glioma-derived mutation. Biochem Biophys Res Commun 390:547–551PubMedCrossRef
73.
go back to reference Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-oncol 1:44–51PubMed Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-oncol 1:44–51PubMed
74.
go back to reference Koos B, Peetz-Dienhart S, Riesmeier B, Fruhwald MC, Hasselblatt M (2010) O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation is significantly less frequent in ependymal tumours as compared to malignant astrocytic gliomas. Neuropathol Appl Neurobiol 36:356–358PubMedCrossRef Koos B, Peetz-Dienhart S, Riesmeier B, Fruhwald MC, Hasselblatt M (2010) O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation is significantly less frequent in ependymal tumours as compared to malignant astrocytic gliomas. Neuropathol Appl Neurobiol 36:356–358PubMedCrossRef
75.
go back to reference Korshunov A, Meyer J, Capper D, Christians A, Remke M, Witt H, Pfister S, von Deimling A, Hartmann C (2009) Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol 118:401–405PubMedCrossRef Korshunov A, Meyer J, Capper D, Christians A, Remke M, Witt H, Pfister S, von Deimling A, Hartmann C (2009) Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol 118:401–405PubMedCrossRef
76.
go back to reference Korshunov A, Witt H, Hielscher T, Benner A, Remke M, Ryzhova M, Milde T, Bender S, Wittmann A, Schottler A, Kulozik AE, Witt O, von Deimling A, Lichter P, Pfister S (2010) Molecular staging of intracranial ependymoma in children and adults. J Clin Oncol 28:3182–3190PubMedCrossRef Korshunov A, Witt H, Hielscher T, Benner A, Remke M, Ryzhova M, Milde T, Bender S, Wittmann A, Schottler A, Kulozik AE, Witt O, von Deimling A, Lichter P, Pfister S (2010) Molecular staging of intracranial ependymoma in children and adults. J Clin Oncol 28:3182–3190PubMedCrossRef
77.
go back to reference Labussiere M, Idbaih A, Wang XW, Marie Y, Boisselier B, Falet C, Paris S, Laffaire J, Carpentier C, Criniere E, Ducray F, El Hallani S, Mokhtari K, Hoang-Xuan K, Delattre JY, Sanson M (2010) All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Neurology 74:1886–1890PubMedCrossRef Labussiere M, Idbaih A, Wang XW, Marie Y, Boisselier B, Falet C, Paris S, Laffaire J, Carpentier C, Criniere E, Ducray F, El Hallani S, Mokhtari K, Hoang-Xuan K, Delattre JY, Sanson M (2010) All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Neurology 74:1886–1890PubMedCrossRef
78.
go back to reference Levin N, Lavon I, Zelikovitsh B, Fuchs D, Bokstein F, Fellig Y, Siegal T (2006) Progressive low-grade oligodendrogliomas: response to temozolomide and correlation between genetic profile and O6-methylguanine DNA methyltransferase protein expression. Cancer 106:1759–1765PubMedCrossRef Levin N, Lavon I, Zelikovitsh B, Fuchs D, Bokstein F, Fellig Y, Siegal T (2006) Progressive low-grade oligodendrogliomas: response to temozolomide and correlation between genetic profile and O6-methylguanine DNA methyltransferase protein expression. Cancer 106:1759–1765PubMedCrossRef
79.
go back to reference Li G, Wong AJ (2008) EGF receptor variant III as a target antigen for tumor immunotherapy. Expert Rev Vaccines 7:977–985PubMedCrossRef Li G, Wong AJ (2008) EGF receptor variant III as a target antigen for tumor immunotherapy. Expert Rev Vaccines 7:977–985PubMedCrossRef
80.
go back to reference Linz U (2010) Commentary on Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial (Lancet Oncol. 2009;10:459-466). Cancer 116:1844–1846PubMedCrossRef Linz U (2010) Commentary on Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial (Lancet Oncol. 2009;10:459-466). Cancer 116:1844–1846PubMedCrossRef
81.
go back to reference Louis DN, Ohgaki H, Wiestler OD, CaveneeWK (eds) (2007) WHO classification of tumours of the central nervous system, 3rd edn. IARC Press, Lyon Louis DN, Ohgaki H, Wiestler OD, CaveneeWK (eds) (2007) WHO classification of tumours of the central nervous system, 3rd edn. IARC Press, Lyon
82.
go back to reference Maxwell JA, Johnson SP, McLendon RE, Lister DW, Horne KS, Rasheed A, Quinn JA, Ali-Osman F, Friedman AH, Modrich PL, Bigner DD, Friedman HS (2008) Mismatch repair deficiency does not mediate clinical resistance to temozolomide in malignant glioma. Clin Cancer Res 14:4859–4868PubMedCrossRef Maxwell JA, Johnson SP, McLendon RE, Lister DW, Horne KS, Rasheed A, Quinn JA, Ali-Osman F, Friedman AH, Modrich PL, Bigner DD, Friedman HS (2008) Mismatch repair deficiency does not mediate clinical resistance to temozolomide in malignant glioma. Clin Cancer Res 14:4859–4868PubMedCrossRef
83.
go back to reference McDonald KL, McDonnell J, Muntoni A, Henson JD, Hegi ME, von Deimling A, Wheeler HR, Cook RJ, Biggs MT, Little NS, Robinson BG, Reddel RR, Royds JA (2010) Presence of alternative lengthening of telomeres mechanism in patients with glioblastoma identifies a less aggressive tumor type with longer survival. J Neuropathol Exp Neurol 69:729–736PubMedCrossRef McDonald KL, McDonnell J, Muntoni A, Henson JD, Hegi ME, von Deimling A, Wheeler HR, Cook RJ, Biggs MT, Little NS, Robinson BG, Reddel RR, Royds JA (2010) Presence of alternative lengthening of telomeres mechanism in patients with glioblastoma identifies a less aggressive tumor type with longer survival. J Neuropathol Exp Neurol 69:729–736PubMedCrossRef
84.
go back to reference McEllin B, Camacho CV, Mukherjee B, Hahm B, Tomimatsu N, Bachoo RM, Burma S (2010) PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors. Cancer Res 70:5457–5464PubMedCrossRef McEllin B, Camacho CV, Mukherjee B, Hahm B, Tomimatsu N, Bachoo RM, Burma S (2010) PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors. Cancer Res 70:5457–5464PubMedCrossRef
85.
go back to reference Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, Mischel PS (2005) Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 353:2012–2024PubMedCrossRef Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, Mischel PS (2005) Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 353:2012–2024PubMedCrossRef
86.
go back to reference Meyer J, Pusch S, Balss J, Capper D, Mueller W, Christians A, Hartmann C, von Deimling A (2010) PCR- and restriction endonuclease-based detection of IDH1 mutations. Brain Pathol 20:298–300PubMedCrossRef Meyer J, Pusch S, Balss J, Capper D, Mueller W, Christians A, Hartmann C, von Deimling A (2010) PCR- and restriction endonuclease-based detection of IDH1 mutations. Brain Pathol 20:298–300PubMedCrossRef
87.
go back to reference Mikeska T, Bock C, El-Maarri O, Hubner A, Ehrentraut D, Schramm J, Felsberg J, Kahl P, Buttner R, Pietsch T, Waha A (2007) Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J Mol Diagn 9:368–381PubMedCrossRef Mikeska T, Bock C, El-Maarri O, Hubner A, Ehrentraut D, Schramm J, Felsberg J, Kahl P, Buttner R, Pietsch T, Waha A (2007) Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J Mol Diagn 9:368–381PubMedCrossRef
88.
go back to reference Mollemann M, Wolter M, Felsberg J, Collins VP, Reifenberger G (2005) Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. Int J Cancer 113:379–385PubMedCrossRef Mollemann M, Wolter M, Felsberg J, Collins VP, Reifenberger G (2005) Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. Int J Cancer 113:379–385PubMedCrossRef
89.
go back to reference Murat A, Migliavacca E, Gorlia T, Lambiv WL, Shay T, Hamou MF, de Tribolet N, Regli L, Wick W, Kouwenhoven MC, Hainfellner JA, Heppner FL, Dietrich PY, Zimmer Y, Cairncross JG, Janzer RC, Domany E, Delorenzi M, Stupp R, Hegi ME (2008) Stem cell-related “self-renewal” signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol 26:3015–3024PubMedCrossRef Murat A, Migliavacca E, Gorlia T, Lambiv WL, Shay T, Hamou MF, de Tribolet N, Regli L, Wick W, Kouwenhoven MC, Hainfellner JA, Heppner FL, Dietrich PY, Zimmer Y, Cairncross JG, Janzer RC, Domany E, Delorenzi M, Stupp R, Hegi ME (2008) Stem cell-related “self-renewal” signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol 26:3015–3024PubMedCrossRef
90.
go back to reference Nobusawa S, Watanabe T, Kleihues P, Ohgaki H (2009) IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 15:6002–6007PubMedCrossRef Nobusawa S, Watanabe T, Kleihues P, Ohgaki H (2009) IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 15:6002–6007PubMedCrossRef
91.
go back to reference Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522PubMedCrossRef Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522PubMedCrossRef
92.
go back to reference Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartmann C, McLaughlin ME, Batchelor TT, Black PM, von Deimling A, Pomeroy SL, Golub TR, Louis DN (2003) Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 63:1602–1607PubMed Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartmann C, McLaughlin ME, Batchelor TT, Black PM, von Deimling A, Pomeroy SL, Golub TR, Louis DN (2003) Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 63:1602–1607PubMed
93.
go back to reference Ohgaki H, Kleihues P (2007) Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170:1445–1453PubMedCrossRef Ohgaki H, Kleihues P (2007) Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170:1445–1453PubMedCrossRef
94.
go back to reference Papait R, Magrassi L, Rigamonti D, Cattaneo E (2009) Temozolomide and carmustine cause large-scale heterochromatin reorganization in glioma cells. Biochem Biophys Res Commun 379:434–439PubMedCrossRef Papait R, Magrassi L, Rigamonti D, Cattaneo E (2009) Temozolomide and carmustine cause large-scale heterochromatin reorganization in glioma cells. Biochem Biophys Res Commun 379:434–439PubMedCrossRef
95.
go back to reference Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812PubMedCrossRef Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812PubMedCrossRef
96.
go back to reference Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J, Bax DA, Coyle B, Barrow J, Hargrave D, Lowe J, Gajjar A, Zhao W, Broniscer A, Ellison DW, Grundy RG, Baker SJ (2010) Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol 28:3061–3068PubMedCrossRef Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J, Bax DA, Coyle B, Barrow J, Hargrave D, Lowe J, Gajjar A, Zhao W, Broniscer A, Ellison DW, Grundy RG, Baker SJ (2010) Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol 28:3061–3068PubMedCrossRef
97.
go back to reference Pelloski CE, Ballman KV, Furth AF, Zhang L, Lin E, Sulman EP, Bhat K, McDonald JM, Yung WK, Colman H, Woo SY, Heimberger AB, Suki D, Prados MD, Chang SM, Barker FG 2nd, Buckner JC, James CD, Aldape K (2007) Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J Clin Oncol 25:2288–2294PubMedCrossRef Pelloski CE, Ballman KV, Furth AF, Zhang L, Lin E, Sulman EP, Bhat K, McDonald JM, Yung WK, Colman H, Woo SY, Heimberger AB, Suki D, Prados MD, Chang SM, Barker FG 2nd, Buckner JC, James CD, Aldape K (2007) Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J Clin Oncol 25:2288–2294PubMedCrossRef
98.
go back to reference Pfister S, Janzarik WG, Remke M, Ernst A, Werft W, Becker N, Toedt G, Wittmann A, Kratz C, Olbrich H, Ahmadi R, Thieme B, Joos S, Radlwimmer B, Kulozik A, Pietsch T, Herold-Mende C, Gnekow A, Reifenberger G, Korshunov A, Scheurlen W, Omran H, Lichter P (2008) BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest 118:1739–1749PubMedCrossRef Pfister S, Janzarik WG, Remke M, Ernst A, Werft W, Becker N, Toedt G, Wittmann A, Kratz C, Olbrich H, Ahmadi R, Thieme B, Joos S, Radlwimmer B, Kulozik A, Pietsch T, Herold-Mende C, Gnekow A, Reifenberger G, Korshunov A, Scheurlen W, Omran H, Lichter P (2008) BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest 118:1739–1749PubMedCrossRef
99.
go back to reference Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157–173PubMedCrossRef Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157–173PubMedCrossRef
100.
go back to reference Pollack IF, Hamilton RL, Sobol RW, Burnham J, Yates AJ, Holmes EJ, Zhou T, Finlay JL (2006) O6-methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 cohort. J Clin Oncol 24:3431–3437PubMedCrossRef Pollack IF, Hamilton RL, Sobol RW, Burnham J, Yates AJ, Holmes EJ, Zhou T, Finlay JL (2006) O6-methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 cohort. J Clin Oncol 24:3431–3437PubMedCrossRef
101.
go back to reference Preusser M, Gelpi E, Rottenfusser A, Dieckmann K, Widhalm G, Dietrich W, Bertalanffy A, Prayer D, Hainfellner JA, Marosi C (2008) Epithelial growth factor receptor inhibitors for treatment of recurrent or progressive high grade glioma: an exploratory study. J Neurooncol 89:211–218PubMedCrossRef Preusser M, Gelpi E, Rottenfusser A, Dieckmann K, Widhalm G, Dietrich W, Bertalanffy A, Prayer D, Hainfellner JA, Marosi C (2008) Epithelial growth factor receptor inhibitors for treatment of recurrent or progressive high grade glioma: an exploratory study. J Neurooncol 89:211–218PubMedCrossRef
102.
go back to reference Reifenberger G, Louis DN (2003) Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 62:111–126PubMed Reifenberger G, Louis DN (2003) Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 62:111–126PubMed
103.
go back to reference Reitman ZJ, Yan H (2010) Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. J Natl Cancer Inst 102:932–941PubMedCrossRef Reitman ZJ, Yan H (2010) Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. J Natl Cancer Inst 102:932–941PubMedCrossRef
104.
go back to reference Rivera AL, Pelloski CE, Gilbert MR, Colman H, De La Cruz C, Sulman EP, Bekele BN, Aldape KD (2010) MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro Oncol 12:116–121PubMed Rivera AL, Pelloski CE, Gilbert MR, Colman H, De La Cruz C, Sulman EP, Bekele BN, Aldape KD (2010) MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro Oncol 12:116–121PubMed
105.
go back to reference Roerig P, Nessling M, Radlwimmer B, Joos S, Wrobel G, Schwaenen C, Reifenberger G, Lichter P (2005) Molecular classification of human gliomas using matrix-based comparative genomic hybridization. Int J Cancer 117:95–103PubMedCrossRef Roerig P, Nessling M, Radlwimmer B, Joos S, Wrobel G, Schwaenen C, Reifenberger G, Lichter P (2005) Molecular classification of human gliomas using matrix-based comparative genomic hybridization. Int J Cancer 117:95–103PubMedCrossRef
106.
go back to reference Rokes CA, Remke M, Guha-Thakurta N, Witt O, Korshunov A, Pfister S and Wolff JE (2010) Sorafenib plus valproic acid for infant spinal glioblastoma. J Pediatr Hematol Oncol Rokes CA, Remke M, Guha-Thakurta N, Witt O, Korshunov A, Pfister S and Wolff JE (2010) Sorafenib plus valproic acid for infant spinal glioblastoma. J Pediatr Hematol Oncol
107.
go back to reference Sampson JH, Archer GE, Mitchell DA, Heimberger AB, Bigner DD (2008) Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma. Semin Immunol 20:267–275PubMedCrossRef Sampson JH, Archer GE, Mitchell DA, Heimberger AB, Bigner DD (2008) Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma. Semin Immunol 20:267–275PubMedCrossRef
108.
go back to reference Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154PubMedCrossRef Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154PubMedCrossRef
109.
go back to reference Scheie D, Cvancarova M, Mork S, Skullerud K, Andresen PA, Benestad I, Helseth E, Meling T, Beiske K (2008) Can morphology predict 1p/19q loss in oligodendroglial tumours? Histopathology 53:578–587PubMedCrossRef Scheie D, Cvancarova M, Mork S, Skullerud K, Andresen PA, Benestad I, Helseth E, Meling T, Beiske K (2008) Can morphology predict 1p/19q loss in oligodendroglial tumours? Histopathology 53:578–587PubMedCrossRef
110.
go back to reference Schlosser S, Wagner S, Muhlisch J, Hasselblatt M, Gerss J, Wolff JE, Fruhwald MC (2010) MGMT as a potential stratification marker in relapsed high-grade glioma of children: the HIT-GBM experience. Pediatr Blood Cancer 54:228–237PubMed Schlosser S, Wagner S, Muhlisch J, Hasselblatt M, Gerss J, Wolff JE, Fruhwald MC (2010) MGMT as a potential stratification marker in relapsed high-grade glioma of children: the HIT-GBM experience. Pediatr Blood Cancer 54:228–237PubMed
111.
go back to reference Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30:e57PubMedCrossRef Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30:e57PubMedCrossRef
112.
go back to reference Seiz M, Tuettenberg J, Meyer J, Essig M, Schmieder K, Mawrin C, von Deimling A, Hartmann C (2010) Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes. Acta Neuropathol 120:261–267PubMedCrossRef Seiz M, Tuettenberg J, Meyer J, Essig M, Schmieder K, Mawrin C, von Deimling A, Hartmann C (2010) Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes. Acta Neuropathol 120:261–267PubMedCrossRef
113.
go back to reference Shinojima N, Tada K, Shiraishi S, Kamiryo T, Kochi M, Nakamura H, Makino K, Saya H, Hirano H, Kuratsu J, Oka K, Ishimaru Y, Ushio Y (2003) Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res 63:6962–6970PubMed Shinojima N, Tada K, Shiraishi S, Kamiryo T, Kochi M, Nakamura H, Makino K, Saya H, Hirano H, Kuratsu J, Oka K, Ishimaru Y, Ushio Y (2003) Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res 63:6962–6970PubMed
114.
go back to reference Smith JS, Alderete B, Minn Y, Borell TJ, Perry A, Mohapatra G, Hosek SM, Kimmel D, O’Fallon J, Yates A, Feuerstein BG, Burger PC, Scheithauer BW, Jenkins RB (1999) Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 18:4144–4152PubMedCrossRef Smith JS, Alderete B, Minn Y, Borell TJ, Perry A, Mohapatra G, Hosek SM, Kimmel D, O’Fallon J, Yates A, Feuerstein BG, Burger PC, Scheithauer BW, Jenkins RB (1999) Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 18:4144–4152PubMedCrossRef
115.
go back to reference Smith JS, Tachibana I, Passe SM, Huntley BK, Borell TJ, Iturria N, O’Fallon JR, Schaefer PL, Scheithauer BW, James CD, Buckner JC, Jenkins RB (2001) PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 93:1246–1256PubMedCrossRef Smith JS, Tachibana I, Passe SM, Huntley BK, Borell TJ, Iturria N, O’Fallon JR, Schaefer PL, Scheithauer BW, James CD, Buckner JC, Jenkins RB (2001) PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 93:1246–1256PubMedCrossRef
116.
go back to reference Sonoda Y, Kumabe T, Nakamura T, Saito R, Kanamori M, Yamashita Y, Suzuki H, Tominaga T (2009) Analysis of IDH1 and IDH2 mutations in Japanese glioma patients. Cancer Sci 100:1996–1998PubMedCrossRef Sonoda Y, Kumabe T, Nakamura T, Saito R, Kanamori M, Yamashita Y, Suzuki H, Tominaga T (2009) Analysis of IDH1 and IDH2 mutations in Japanese glioma patients. Cancer Sci 100:1996–1998PubMedCrossRef
117.
go back to reference Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef
118.
go back to reference Sugawa N, Ekstrand AJ, James CD, Collins VP (1990) Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci USA 87:8602–8606PubMedCrossRef Sugawa N, Ekstrand AJ, James CD, Collins VP (1990) Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci USA 87:8602–8606PubMedCrossRef
119.
go back to reference Tentori L, Leonetti C, Scarsella M, D’Amati G, Vergati M, Portarena I, Xu W, Kalish V, Zupi G, Zhang J, Graziani G (2003) Systemic administration of GPI 15427, a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumor activity of temozolomide against intracranial melanoma, glioma, lymphoma. Clin Cancer Res 9:5370–5379PubMed Tentori L, Leonetti C, Scarsella M, D’Amati G, Vergati M, Portarena I, Xu W, Kalish V, Zupi G, Zhang J, Graziani G (2003) Systemic administration of GPI 15427, a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumor activity of temozolomide against intracranial melanoma, glioma, lymphoma. Clin Cancer Res 9:5370–5379PubMed
120.
go back to reference Toedt G, Barbus S, Wolter M, Felsberg J, Tews B, Blond F, Sabel MC, Hofmann S, Becker N, Hartmann C, Ohgaki H, von Deimling A, Wiestler OD, Hahn M, Lichter P, Reifenberger G, Radlwimmer B (2010) Molecular signatures classify astrocytic gliomas by IDH1 mutation status. Int J Cancer Toedt G, Barbus S, Wolter M, Felsberg J, Tews B, Blond F, Sabel MC, Hofmann S, Becker N, Hartmann C, Ohgaki H, von Deimling A, Wiestler OD, Hahn M, Lichter P, Reifenberger G, Radlwimmer B (2010) Molecular signatures classify astrocytic gliomas by IDH1 mutation status. Int J Cancer
121.
go back to reference Trost D, Ehrler M, Fimmers R, Felsberg J, Sabel MC, Kirsch L, Schramm J, Wiestler OD, Reifenberger G, Weber RG (2007) Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors. Int J Cancer 120:2368–2376PubMedCrossRef Trost D, Ehrler M, Fimmers R, Felsberg J, Sabel MC, Kirsch L, Schramm J, Wiestler OD, Reifenberger G, Weber RG (2007) Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors. Int J Cancer 120:2368–2376PubMedCrossRef
122.
go back to reference van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T (2006) Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 24:2715–2722PubMedCrossRef van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T (2006) Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 24:2715–2722PubMedCrossRef
123.
go back to reference van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P, Frenay M, Tijssen CC, Lacombe D, Idbaih A, van Marion R, Kros JM, Dinjens WN, Gorlia T, Sanson M (2010) IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res 16:1597–1604PubMedCrossRef van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P, Frenay M, Tijssen CC, Lacombe D, Idbaih A, van Marion R, Kros JM, Dinjens WN, Gorlia T, Sanson M (2010) IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res 16:1597–1604PubMedCrossRef
124.
go back to reference van den Bent MJ, Dubbink HJ, Sanson M, van der Lee-Haarloo CR, Hegi M, Jeuken JW, Ibdaih A, Brandes AA, Taphoorn MJ, Frenay M, Lacombe D, Gorlia T, Dinjens WN, Kros JM (2009) MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol 27:5881–5886PubMedCrossRef van den Bent MJ, Dubbink HJ, Sanson M, van der Lee-Haarloo CR, Hegi M, Jeuken JW, Ibdaih A, Brandes AA, Taphoorn MJ, Frenay M, Lacombe D, Gorlia T, Dinjens WN, Kros JM (2009) MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol 27:5881–5886PubMedCrossRef
125.
go back to reference van den Bent MJ, Looijenga LH, Langenberg K, Dinjens W, Graveland W, Uytdewilligen L, Sillevis Smitt PA, Jenkins RB, Kros JM (2003) Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features. Cancer 97:1276–1284PubMedCrossRef van den Bent MJ, Looijenga LH, Langenberg K, Dinjens W, Graveland W, Uytdewilligen L, Sillevis Smitt PA, Jenkins RB, Kros JM (2003) Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features. Cancer 97:1276–1284PubMedCrossRef
126.
go back to reference Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110PubMedCrossRef Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110PubMedCrossRef
127.
go back to reference Vlassenbroeck I, Califice S, Diserens AC, Migliavacca E, Straub J, Di Stefano I, Moreau F, Hamou MF, Renard I, Delorenzi M, Flamion B, DiGuiseppi J, Bierau K, Hegi ME (2008) Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn 10:332–337PubMedCrossRef Vlassenbroeck I, Califice S, Diserens AC, Migliavacca E, Straub J, Di Stefano I, Moreau F, Hamou MF, Renard I, Delorenzi M, Flamion B, DiGuiseppi J, Bierau K, Hegi ME (2008) Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn 10:332–337PubMedCrossRef
128.
go back to reference Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE, Rabinowitz JD, Carroll M, Su SM, Sharp KA, Levine RL, Thompson CB (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:225–234PubMedCrossRef Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE, Rabinowitz JD, Carroll M, Su SM, Sharp KA, Levine RL, Thompson CB (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:225–234PubMedCrossRef
129.
go back to reference Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153PubMedCrossRef Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153PubMedCrossRef
130.
go back to reference Watanabe T, Vital A, Nobusawa S, Kleihues P, Ohgaki H (2009) Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome. Acta Neuropathol 117:653–656PubMedCrossRef Watanabe T, Vital A, Nobusawa S, Kleihues P, Ohgaki H (2009) Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome. Acta Neuropathol 117:653–656PubMedCrossRef
131.
go back to reference Weller M, Berger H, Hartmann C, Schramm J, Westphal M, Simon M, Goldbrunner R, Krex D, Steinbach JP, Ostertag CB, Loeffler M, Pietsch T, von Deimling A (2007) Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker? Clin Cancer Res 13:6933–6937PubMedCrossRef Weller M, Berger H, Hartmann C, Schramm J, Westphal M, Simon M, Goldbrunner R, Krex D, Steinbach JP, Ostertag CB, Loeffler M, Pietsch T, von Deimling A (2007) Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker? Clin Cancer Res 13:6933–6937PubMedCrossRef
132.
go back to reference Weller M, Felsberg J, Hartmann C, Berger H, Steinbach JP, Schramm J, Westphal M, Schackert G, Simon M, Tonn JC, Heese O, Krex D, Nikkhah G, Pietsch T, Wiestler O, Reifenberger G, von Deimling A, Loeffler M (2009) Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol 27:5743–5750PubMedCrossRef Weller M, Felsberg J, Hartmann C, Berger H, Steinbach JP, Schramm J, Westphal M, Schackert G, Simon M, Tonn JC, Heese O, Krex D, Nikkhah G, Pietsch T, Wiestler O, Reifenberger G, von Deimling A, Loeffler M (2009) Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol 27:5743–5750PubMedCrossRef
133.
go back to reference Weller M, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, Hegi ME (2010) MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol 6:39–51PubMedCrossRef Weller M, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, Hegi ME (2010) MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol 6:39–51PubMedCrossRef
134.
go back to reference Weppler SA, Li Y, Dubois L, Lieuwes N, Jutten B, Lambin P, Wouters BG, Lammering G (2007) Expression of EGFR variant vIII promotes both radiation resistance and hypoxia tolerance. Radiother Oncol 83:333–339PubMedCrossRef Weppler SA, Li Y, Dubois L, Lieuwes N, Jutten B, Lambin P, Wouters BG, Lammering G (2007) Expression of EGFR variant vIII promotes both radiation resistance and hypoxia tolerance. Radiother Oncol 83:333–339PubMedCrossRef
135.
go back to reference Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27:5874–5880PubMedCrossRef Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27:5874–5880PubMedCrossRef
136.
go back to reference Wikstrand CJ, Hale LP, Batra SK, Hill ML, Humphrey PA, Kurpad SN, McLendon RE, Moscatello D, Pegram CN, Reist CJ et al (1995) Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas. Cancer Res 55:3140–3148PubMed Wikstrand CJ, Hale LP, Batra SK, Hill ML, Humphrey PA, Kurpad SN, McLendon RE, Moscatello D, Pegram CN, Reist CJ et al (1995) Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas. Cancer Res 55:3140–3148PubMed
137.
go back to reference Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773PubMedCrossRef Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773PubMedCrossRef
138.
go back to reference Yip S, Iafrate AJ, Louis DN (2008) Molecular diagnostic testing in malignant gliomas: a practical update on predictive markers. J Neuropathol Exp Neurol 67:1–15PubMedCrossRef Yip S, Iafrate AJ, Louis DN (2008) Molecular diagnostic testing in malignant gliomas: a practical update on predictive markers. J Neuropathol Exp Neurol 67:1–15PubMedCrossRef
139.
go back to reference Yip S, Miao J, Cahill DP, Iafrate AJ, Aldape K, Nutt CL, Louis DN (2009) MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin Cancer Res 15:4622–4629PubMedCrossRef Yip S, Miao J, Cahill DP, Iafrate AJ, Aldape K, Nutt CL, Louis DN (2009) MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin Cancer Res 15:4622–4629PubMedCrossRef
140.
go back to reference Yoshimoto K, Dang J, Zhu S, Nathanson D, Huang T, Dumont R, Seligson DB, Yong WH, Xiong Z, Rao N, Winther H, Chakravarti A, Bigner DD, Mellinghoff IK, Horvath S, Cavenee WK, Cloughesy TF, Mischel PS (2008) Development of a real-time RT-PCR assay for detecting EGFRvIII in glioblastoma samples. Clin Cancer Res 14:488–493PubMedCrossRef Yoshimoto K, Dang J, Zhu S, Nathanson D, Huang T, Dumont R, Seligson DB, Yong WH, Xiong Z, Rao N, Winther H, Chakravarti A, Bigner DD, Mellinghoff IK, Horvath S, Cavenee WK, Cloughesy TF, Mischel PS (2008) Development of a real-time RT-PCR assay for detecting EGFRvIII in glioblastoma samples. Clin Cancer Res 14:488–493PubMedCrossRef
141.
go back to reference Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, Yu W, Li Z, Gong L, Peng Y, Ding J, Lei Q, Guan KL, Xiong Y (2009) Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1α. Science 324:261–265PubMedCrossRef Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, Yu W, Li Z, Gong L, Peng Y, Ding J, Lei Q, Guan KL, Xiong Y (2009) Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1α. Science 324:261–265PubMedCrossRef
Metadata
Title
Molecular diagnostics of gliomas: state of the art
Authors
Markus J. Riemenschneider
Judith W. M. Jeuken
Pieter Wesseling
Guido Reifenberger
Publication date
01-11-2010
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 5/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-010-0736-4

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