Skip to main content
Top
Published in: Current Oncology Reports 2/2012

01-04-2012 | Pediatric Oncology (S Epelman, Section Editor)

Impact of Molecular Biology Studies on the Understanding of Brain Tumors in Childhood

Authors: Amulya A. Nageswara Rao, Roger J. Packer

Published in: Current Oncology Reports | Issue 2/2012

Login to get access

Abstract

Pediatric brain tumors are the second most common form of childhood malignancy. Brain tumors are a very heterogenous group of tumors and the pathogenesis of many of these tumors is yet to be clearly elucidated. Current diagnostic tools include histopathology and immunohistochemistry, but classification based on these means has significant limitations. As our understanding of the molecular biology of individual tumors continues to increase it has led to the identification of reliable and increasingly available molecular biomarkers. Molecular techniques are likely to complement current standard means of investigation and help not only overcome diagnostic challenges but may also result in better disease classification and risk stratification, leading to more personalized therapeutic approaches.
Literature
1.
go back to reference CBTRUS. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004-2007. Source: Central Brain Tumor Registry of the United States, Hinsdale, IL website: wwwcbtrusorg (2011). CBTRUS. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004-2007. Source: Central Brain Tumor Registry of the United States, Hinsdale, IL website: wwwcbtrusorg (2011).
2.
go back to reference Armstrong GT, Stovall M, Robison LL. Long-term effects of radiation exposure among adult survivors of childhood cancer: results from the childhood cancer survivor study. Radiat Res. 2010;174(6):840–50.PubMedCrossRef Armstrong GT, Stovall M, Robison LL. Long-term effects of radiation exposure among adult survivors of childhood cancer: results from the childhood cancer survivor study. Radiat Res. 2010;174(6):840–50.PubMedCrossRef
3.
go back to reference Turner CD, Rey-Casserly C, Liptak CC, et al. Late effects of therapy for pediatric brain tumor survivors. J Child Neurol. 2009;24(11):1455–63.PubMedCrossRef Turner CD, Rey-Casserly C, Liptak CC, et al. Late effects of therapy for pediatric brain tumor survivors. J Child Neurol. 2009;24(11):1455–63.PubMedCrossRef
4.
go back to reference Crawford JR, MacDonald TJ, Packer RJ. Medulloblastoma in childhood: new biological advances. Lancet Neurol. 2007;6(12):1073–85.PubMedCrossRef Crawford JR, MacDonald TJ, Packer RJ. Medulloblastoma in childhood: new biological advances. Lancet Neurol. 2007;6(12):1073–85.PubMedCrossRef
5.
go back to reference Packer RJ, Rood BR, MacDonald TJ. Medulloblastoma: present concepts of stratification into risk groups. Pediatr Neurosurg. 2003;39(2):60–7.PubMedCrossRef Packer RJ, Rood BR, MacDonald TJ. Medulloblastoma: present concepts of stratification into risk groups. Pediatr Neurosurg. 2003;39(2):60–7.PubMedCrossRef
6.
go back to reference Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.PubMedCrossRef Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.PubMedCrossRef
7.
go back to reference Leary SE, Zhou T, Holmes E, et al. Histology predicts a favorable outcome in young children with desmoplastic medulloblastoma: a report from the children’s oncology group. Cancer. 2011;117(14):3262–7.PubMedCrossRef Leary SE, Zhou T, Holmes E, et al. Histology predicts a favorable outcome in young children with desmoplastic medulloblastoma: a report from the children’s oncology group. Cancer. 2011;117(14):3262–7.PubMedCrossRef
8.
go back to reference Rutkowski S, von Hoff K, Emser A, et al. Survival and prognostic factors of early childhood medulloblastoma: an international meta-analysis. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2010;28(33):4961–8.PubMedCrossRef Rutkowski S, von Hoff K, Emser A, et al. Survival and prognostic factors of early childhood medulloblastoma: an international meta-analysis. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2010;28(33):4961–8.PubMedCrossRef
9.
go back to reference von Hoff K, Hartmann W, von Bueren AO, et al. Large cell/anaplastic medulloblastoma: outcome according to myc status, histopathological, and clinical risk factors. Pediatr Blood Cancer. 2010;54(3):369–76.CrossRef von Hoff K, Hartmann W, von Bueren AO, et al. Large cell/anaplastic medulloblastoma: outcome according to myc status, histopathological, and clinical risk factors. Pediatr Blood Cancer. 2010;54(3):369–76.CrossRef
10.
go back to reference Giangaspero F, Wellek S, Masuoka J, et al. Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol. 2006;112(1):5–12.PubMedCrossRef Giangaspero F, Wellek S, Masuoka J, et al. Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol. 2006;112(1):5–12.PubMedCrossRef
11.
go back to reference Lamont JM, McManamy CS, Pearson AD, et al. Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2004;10(16):5482–93.PubMedCrossRef Lamont JM, McManamy CS, Pearson AD, et al. Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2004;10(16):5482–93.PubMedCrossRef
12.
go back to reference Pan E, Pellarin M, Holmes E, et al. Isochromosome 17q is a negative prognostic factor in poor-risk childhood medulloblastoma patients. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2005;11(13):4733–40.PubMedCrossRef Pan E, Pellarin M, Holmes E, et al. Isochromosome 17q is a negative prognostic factor in poor-risk childhood medulloblastoma patients. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2005;11(13):4733–40.PubMedCrossRef
13.
go back to reference Pfister S, Remke M, Benner A, et al. Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2009;27(10):1627–36.PubMedCrossRef Pfister S, Remke M, Benner A, et al. Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2009;27(10):1627–36.PubMedCrossRef
14.
go back to reference Northcott PA, Nakahara Y, Wu X, et al. Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nat Genet. 2009;41(4):465–72.PubMedCrossRef Northcott PA, Nakahara Y, Wu X, et al. Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nat Genet. 2009;41(4):465–72.PubMedCrossRef
15.
go back to reference Stearns D, Chaudhry A, Abel TW, et al. c-myc overexpression causes anaplasia in medulloblastoma. Cancer Res. 2006;66(2):673–81.PubMedCrossRef Stearns D, Chaudhry A, Abel TW, et al. c-myc overexpression causes anaplasia in medulloblastoma. Cancer Res. 2006;66(2):673–81.PubMedCrossRef
16.
go back to reference Eberhart CG, Kratz J, Wang Y, et al. Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol. 2004;63(5):441–9.PubMed Eberhart CG, Kratz J, Wang Y, et al. Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol. 2004;63(5):441–9.PubMed
17.
go back to reference Pfaff E, Remke M, Sturm D, et al. TP53 mutation is frequently associated with CTNNB1 mutation or MYCN amplification and is compatible with long-term survival in medulloblastoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2010;28(35):5188–96.PubMedCrossRef Pfaff E, Remke M, Sturm D, et al. TP53 mutation is frequently associated with CTNNB1 mutation or MYCN amplification and is compatible with long-term survival in medulloblastoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2010;28(35):5188–96.PubMedCrossRef
18.
go back to reference Mendrzyk F, Radlwimmer B, Joos S, et al. Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2005;23(34):8853–62.PubMedCrossRef Mendrzyk F, Radlwimmer B, Joos S, et al. Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2005;23(34):8853–62.PubMedCrossRef
19.
go back to reference Eberhart CG, Kratz JE, Schuster A, et al. Comparative genomic hybridization detects an increased number of chromosomal alterations in large cell/anaplastic medulloblastomas. Brain Pathol. 2002;12(1):36–44.PubMedCrossRef Eberhart CG, Kratz JE, Schuster A, et al. Comparative genomic hybridization detects an increased number of chromosomal alterations in large cell/anaplastic medulloblastomas. Brain Pathol. 2002;12(1):36–44.PubMedCrossRef
20.
go back to reference Di C, Liao S, Adamson DC, et al. Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid. Cancer Res. 2005;65(3):919–24.PubMed Di C, Liao S, Adamson DC, et al. Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid. Cancer Res. 2005;65(3):919–24.PubMed
21.
go back to reference Crawford JR, Rood BR, Rossi CT, et al. Medulloblastoma associated with novel PTCH mutation as primary manifestation of Gorlin syndrome. Neurology. 2009;72(18):1618.PubMedCrossRef Crawford JR, Rood BR, Rossi CT, et al. Medulloblastoma associated with novel PTCH mutation as primary manifestation of Gorlin syndrome. Neurology. 2009;72(18):1618.PubMedCrossRef
22.
go back to reference •• Ellison DW, Dalton J, Kocak M, et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta neuropathologica 2011:121(3):381-396. This study describes the clinicopathologic data of the SHH, WNT, and SHH/WNT molecular subgroups of medulloblastoma based on a clinical trial cohort. •• Ellison DW, Dalton J, Kocak M, et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta neuropathologica 2011:121(3):381-396. This study describes the clinicopathologic data of the SHH, WNT, and SHH/WNT molecular subgroups of medulloblastoma based on a clinical trial cohort.
23.
go back to reference Zurawel RH, Allen C, Chiappa S, et al. Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma. Genes Chromosomes Cancer. 2000;27(1):44–51.PubMedCrossRef Zurawel RH, Allen C, Chiappa S, et al. Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma. Genes Chromosomes Cancer. 2000;27(1):44–51.PubMedCrossRef
24.
go back to reference McLaughlin MR, Gollin SM, Lese CM, et al. Medulloblastoma and glioblastoma multiforme in a patient with Turcot syndrome: a case report. Surg Neurol. 1998;49(3):295–301.PubMedCrossRef McLaughlin MR, Gollin SM, Lese CM, et al. Medulloblastoma and glioblastoma multiforme in a patient with Turcot syndrome: a case report. Surg Neurol. 1998;49(3):295–301.PubMedCrossRef
25.
go back to reference Dahmen RP, Koch A, Denkhaus D, et al. Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas. Cancer Res. 2001;61(19):7039–43.PubMed Dahmen RP, Koch A, Denkhaus D, et al. Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas. Cancer Res. 2001;61(19):7039–43.PubMed
26.
go back to reference McMahon AP, Bradley A. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell. 1990;62(6):1073–85.PubMedCrossRef McMahon AP, Bradley A. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell. 1990;62(6):1073–85.PubMedCrossRef
27.
go back to reference Hayden MA, Akong K, Peifer M. Novel roles for APC family members and Wingless/Wnt signaling during Drosophila brain development. Dev Biol. 2007;305(1):358–76.PubMedCrossRef Hayden MA, Akong K, Peifer M. Novel roles for APC family members and Wingless/Wnt signaling during Drosophila brain development. Dev Biol. 2007;305(1):358–76.PubMedCrossRef
28.
go back to reference • Fattet S, Haberler C, Legoix P, et al. Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics. The Journal of pathology 2009:218(1):86-94. CTNNB1-mutated tumours represent a distinct molecular subgroup of medulloblastomas with favourable outcome. • Fattet S, Haberler C, Legoix P, et al. Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics. The Journal of pathology 2009:218(1):86-94. CTNNB1-mutated tumours represent a distinct molecular subgroup of medulloblastomas with favourable outcome.
29.
go back to reference Gibson P, Tong Y, Robinson G, et al. Subtypes of medulloblastoma have distinct developmental origins. Nature. 2010;468(7327):1095–9.PubMedCrossRef Gibson P, Tong Y, Robinson G, et al. Subtypes of medulloblastoma have distinct developmental origins. Nature. 2010;468(7327):1095–9.PubMedCrossRef
30.
go back to reference Thompson MC, Fuller C, Hogg TL, et al. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2006;24(12):1924–31.PubMedCrossRef Thompson MC, Fuller C, Hogg TL, et al. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2006;24(12):1924–31.PubMedCrossRef
31.
go back to reference Yokota N, Nishizawa S, Ohta S, et al. Role of Wnt pathway in medulloblastoma oncogenesis. International journal of cancer Journal international du cancer. Int J Cancer. 2002;101(2):198–201.PubMedCrossRef Yokota N, Nishizawa S, Ohta S, et al. Role of Wnt pathway in medulloblastoma oncogenesis. International journal of cancer Journal international du cancer. Int J Cancer. 2002;101(2):198–201.PubMedCrossRef
32.
go back to reference Ellison DW, Onilude OE, Lindsey JC, et al. beta-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children’s Cancer Study Group Brain Tumour Committee. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2005;23(31):7951–7.PubMedCrossRef Ellison DW, Onilude OE, Lindsey JC, et al. beta-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children’s Cancer Study Group Brain Tumour Committee. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2005;23(31):7951–7.PubMedCrossRef
33.
go back to reference de Bont JM, Packer RJ, Michiels EM, et al. Biological background of pediatric medulloblastoma and ependymoma: a review from a translational research perspective. Neuro Oncol. 2008;10(6):1040–60.PubMedCrossRef de Bont JM, Packer RJ, Michiels EM, et al. Biological background of pediatric medulloblastoma and ependymoma: a review from a translational research perspective. Neuro Oncol. 2008;10(6):1040–60.PubMedCrossRef
34.
go back to reference Xu P, Pu PY, Kang CS, et al. Differential expression of Notch1 and Notch2 in astrocytoma and medulloblastoma. Zhonghua bing li xue za zhi Chinese journal of pathology. 2008;37(7):450–3.PubMed Xu P, Pu PY, Kang CS, et al. Differential expression of Notch1 and Notch2 in astrocytoma and medulloblastoma. Zhonghua bing li xue za zhi Chinese journal of pathology. 2008;37(7):450–3.PubMed
35.
go back to reference Shih Ie M, Wang TL. Notch signaling, gamma-secretase inhibitors, and cancer therapy. Cancer Res. 2007;67(5):1879–82.PubMedCrossRef Shih Ie M, Wang TL. Notch signaling, gamma-secretase inhibitors, and cancer therapy. Cancer Res. 2007;67(5):1879–82.PubMedCrossRef
36.
go back to reference Gilbertson RJ, Pearson AD, Perry RH, et al. Prognostic significance of the c-erbB-2 oncogene product in childhood medulloblastoma. Br J Cancer. 1995;71(3):473–7.PubMedCrossRef Gilbertson RJ, Pearson AD, Perry RH, et al. Prognostic significance of the c-erbB-2 oncogene product in childhood medulloblastoma. Br J Cancer. 1995;71(3):473–7.PubMedCrossRef
37.
go back to reference Gilbertson RJ, Clifford SC. PDGFRB is overexpressed in metastatic medulloblastoma. Nat Genet. 2003;35(3):197–8.PubMedCrossRef Gilbertson RJ, Clifford SC. PDGFRB is overexpressed in metastatic medulloblastoma. Nat Genet. 2003;35(3):197–8.PubMedCrossRef
38.
go back to reference Grotzer MA, Janss AJ, Phillips PC, et al. Neurotrophin receptor TrkC predicts good clinical outcome in medulloblastoma and other primitive neuroectodermal brain tumors. Klin Padiatr. 2000;212(4):196–9.PubMedCrossRef Grotzer MA, Janss AJ, Phillips PC, et al. Neurotrophin receptor TrkC predicts good clinical outcome in medulloblastoma and other primitive neuroectodermal brain tumors. Klin Padiatr. 2000;212(4):196–9.PubMedCrossRef
39.
go back to reference •• Northcott PA, Korshunov A, Witt H, et al. Medulloblastoma comprises four distinct molecular variants. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011:29(11):1408-1414. Four molecular subgroups of medulloblastoma were identified using an integrated genomic approach and the use of immunohistochemistry for classifying the four subgroups has been described. •• Northcott PA, Korshunov A, Witt H, et al. Medulloblastoma comprises four distinct molecular variants. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011:29(11):1408-1414. Four molecular subgroups of medulloblastoma were identified using an integrated genomic approach and the use of immunohistochemistry for classifying the four subgroups has been described.
40.
go back to reference Kool M, Koster J, Bunt J, et al. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One. 2008;3(8):e3088.PubMedCrossRef Kool M, Koster J, Bunt J, et al. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One. 2008;3(8):e3088.PubMedCrossRef
41.
go back to reference Cho YJ, Tsherniak A, Tamayo P, et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2011;29(11):1424–30.PubMedCrossRef Cho YJ, Tsherniak A, Tamayo P, et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2011;29(11):1424–30.PubMedCrossRef
42.
go back to reference Curran EK, Sainani KL, Le GM, et al. Gender affects survival for medulloblastoma only in older children and adults: a study from the Surveillance Epidemiology and End Results Registry. Pediatr Blood Cancer. 2009;52(1):60–4.PubMedCrossRef Curran EK, Sainani KL, Le GM, et al. Gender affects survival for medulloblastoma only in older children and adults: a study from the Surveillance Epidemiology and End Results Registry. Pediatr Blood Cancer. 2009;52(1):60–4.PubMedCrossRef
43.
go back to reference Biegel JA. Molecular genetics of atypical teratoid/rhabdoid tumor. Neurosurg Focus. 2006;20(1):E11.PubMedCrossRef Biegel JA. Molecular genetics of atypical teratoid/rhabdoid tumor. Neurosurg Focus. 2006;20(1):E11.PubMedCrossRef
44.
go back to reference Rorke LB, Packer RJ, Biegel JA. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg. 1996;85(1):56–65.PubMedCrossRef Rorke LB, Packer RJ, Biegel JA. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg. 1996;85(1):56–65.PubMedCrossRef
45.
go back to reference Biegel JA, Kalpana G, Knudsen ES, et al. The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors. Cancer Res. 2002;62(1):323–8.PubMed Biegel JA, Kalpana G, Knudsen ES, et al. The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors. Cancer Res. 2002;62(1):323–8.PubMed
46.
go back to reference Versteege I, Sevenet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394(6689):203–6.PubMedCrossRef Versteege I, Sevenet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394(6689):203–6.PubMedCrossRef
47.
go back to reference Biegel JA, Tan L, Zhang F, et al. Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2002;8(11):3461–7.PubMed Biegel JA, Tan L, Zhang F, et al. Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2002;8(11):3461–7.PubMed
48.
go back to reference Janson K, Nedzi LA, David O, et al. Predisposition to atypical teratoid/rhabdoid tumor due to an inherited INI1 mutation. Pediatr Blood Cancer. 2006;47(3):279–84.PubMedCrossRef Janson K, Nedzi LA, David O, et al. Predisposition to atypical teratoid/rhabdoid tumor due to an inherited INI1 mutation. Pediatr Blood Cancer. 2006;47(3):279–84.PubMedCrossRef
49.
go back to reference Biegel JA, Fogelgren B, Wainwright LM, et al. Germline INI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor. Genes Chromosomes Cancer. 2000;28(1):31–7.PubMedCrossRef Biegel JA, Fogelgren B, Wainwright LM, et al. Germline INI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor. Genes Chromosomes Cancer. 2000;28(1):31–7.PubMedCrossRef
50.
go back to reference Judkins AR, Burger PC, Hamilton RL, et al. INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma. J Neuropathol Exp Neurol. 2005;64(5):391–7.PubMed Judkins AR, Burger PC, Hamilton RL, et al. INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma. J Neuropathol Exp Neurol. 2005;64(5):391–7.PubMed
51.
go back to reference Haberler C, Laggner U, Slavc I, et al. Immunohistochemical analysis of INI1 protein in malignant pediatric CNS tumors: Lack of INI1 in atypical teratoid/rhabdoid tumors and in a fraction of primitive neuroectodermal tumors without rhabdoid phenotype. Am J Surg Pathol. 2006;30(11):1462–8.PubMedCrossRef Haberler C, Laggner U, Slavc I, et al. Immunohistochemical analysis of INI1 protein in malignant pediatric CNS tumors: Lack of INI1 in atypical teratoid/rhabdoid tumors and in a fraction of primitive neuroectodermal tumors without rhabdoid phenotype. Am J Surg Pathol. 2006;30(11):1462–8.PubMedCrossRef
52.
go back to reference Hasselblatt M, Gesk S, Oyen F, et al. Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression. Am J Surg Pathol. 2011;35(6):933–5.PubMedCrossRef Hasselblatt M, Gesk S, Oyen F, et al. Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression. Am J Surg Pathol. 2011;35(6):933–5.PubMedCrossRef
53.
go back to reference Schneppenheim R, Fruhwald MC, Gesk S, et al. Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Am J Hum Genet. 2010;86(2):279–84.PubMedCrossRef Schneppenheim R, Fruhwald MC, Gesk S, et al. Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Am J Hum Genet. 2010;86(2):279–84.PubMedCrossRef
54.
go back to reference Birks DK, Kleinschmidt-DeMasters BK, Donson AM, et al. Claudin 6 is a positive marker for atypical teratoid/rhabdoid tumors. Brain Pathol. 2010;20(1):140–50.PubMedCrossRef Birks DK, Kleinschmidt-DeMasters BK, Donson AM, et al. Claudin 6 is a positive marker for atypical teratoid/rhabdoid tumors. Brain Pathol. 2010;20(1):140–50.PubMedCrossRef
55.
go back to reference Gessi M, Giangaspero F, Lauriola L, et al. Embryonal tumors with abundant neuropil and true rosettes: a distinctive CNS primitive neuroectodermal tumor. Am J Surg Pathol. 2009;33(2):211–7.PubMedCrossRef Gessi M, Giangaspero F, Lauriola L, et al. Embryonal tumors with abundant neuropil and true rosettes: a distinctive CNS primitive neuroectodermal tumor. Am J Surg Pathol. 2009;33(2):211–7.PubMedCrossRef
56.
go back to reference Wang Y, Chu SG, Xiong J, et al. Embryonal tumor with abundant neuropil and true rosettes (ETANTR) with a focal amplification at chromosome 19q13.42 locus: further evidence of two new instances in China. Neuropathology : official journal of the Japanese Society of Neuropathology 2011. Wang Y, Chu SG, Xiong J, et al. Embryonal tumor with abundant neuropil and true rosettes (ETANTR) with a focal amplification at chromosome 19q13.42 locus: further evidence of two new instances in China. Neuropathology : official journal of the Japanese Society of Neuropathology 2011.
57.
go back to reference Pfister S, Remke M, Castoldi M, et al. Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes. Acta Neuropathol. 2009;117(4):457–64.PubMedCrossRef Pfister S, Remke M, Castoldi M, et al. Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes. Acta Neuropathol. 2009;117(4):457–64.PubMedCrossRef
58.
go back to reference Korshunov A, Remke M, Gessi M, et al. Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes. Acta Neuropathol. 2010;120(2):253–60.PubMedCrossRef Korshunov A, Remke M, Gessi M, et al. Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes. Acta Neuropathol. 2010;120(2):253–60.PubMedCrossRef
59.
go back to reference Cheng Y, Pang JC, Ng HK, et al. Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas. Histopathology. 2000;37(5):437–44.PubMedCrossRef Cheng Y, Pang JC, Ng HK, et al. Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas. Histopathology. 2000;37(5):437–44.PubMedCrossRef
60.
go back to reference Sanoudou D, Tingby O, Ferguson-Smith MA, et al. Analysis of pilocytic astrocytoma by comparative genomic hybridization. Br J Cancer. 2000;82(6):1218–22.PubMedCrossRef Sanoudou D, Tingby O, Ferguson-Smith MA, et al. Analysis of pilocytic astrocytoma by comparative genomic hybridization. Br J Cancer. 2000;82(6):1218–22.PubMedCrossRef
61.
go back to reference Pfister S, Janzarik WG, Remke M, et al. BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest. 2008;118(5):1739–49.PubMedCrossRef Pfister S, Janzarik WG, Remke M, et al. BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest. 2008;118(5):1739–49.PubMedCrossRef
62.
go back to reference Sievert AJ, Jackson EM, Gai X, et al. Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene. Brain Pathol. 2009;19(3):449–58.PubMedCrossRef Sievert AJ, Jackson EM, Gai X, et al. Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene. Brain Pathol. 2009;19(3):449–58.PubMedCrossRef
63.
go back to reference •• Schindler G, Capper D, Meyer J, et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta neuropathologica 2011:121(3):397-405. This study shows a high association of the BRAFV600E mutation in pleomorphic xanthoastrocytomas, gangliogliomas, and extra-cerebellar pilocytic astrocytomas. BRAFV600E mutation may play a role as a potential diagnostic marker and may pave the way for use of targeted therapeutics in future clinical trials with these tumors. •• Schindler G, Capper D, Meyer J, et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta neuropathologica 2011:121(3):397-405. This study shows a high association of the BRAFV600E mutation in pleomorphic xanthoastrocytomas, gangliogliomas, and extra-cerebellar pilocytic astrocytomas. BRAFV600E mutation may play a role as a potential diagnostic marker and may pave the way for use of targeted therapeutics in future clinical trials with these tumors.
64.
go back to reference Cin H, Meyer C, Herr R, et al. Oncogenic FAM131B-BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma. Acta Neuropathol. 2011;121(6):763–74.PubMedCrossRef Cin H, Meyer C, Herr R, et al. Oncogenic FAM131B-BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma. Acta Neuropathol. 2011;121(6):763–74.PubMedCrossRef
65.
go back to reference Viana-Pereira M, Lopes JM, Little S, et al. Analysis of EGFR overexpression, EGFR gene amplification and the EGFRvIII mutation in Portuguese high-grade gliomas. Anticancer research 2008:28(2A):913-920. Viana-Pereira M, Lopes JM, Little S, et al. Analysis of EGFR overexpression, EGFR gene amplification and the EGFRvIII mutation in Portuguese high-grade gliomas. Anticancer research 2008:28(2A):913-920.
66.
go back to reference Liang ML, Ma J, Ho M, et al. Tyrosine kinase expression in pediatric high grade astrocytoma. J Neurooncol. 2008;87(3):247–53.PubMedCrossRef Liang ML, Ma J, Ho M, et al. Tyrosine kinase expression in pediatric high grade astrocytoma. J Neurooncol. 2008;87(3):247–53.PubMedCrossRef
67.
go back to reference Bax DA, Gaspar N, Little SE, et al. EGFRvIII deletion mutations in pediatric high-grade glioma and response to targeted therapy in pediatric glioma cell lines. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2009;15(18):5753–61.PubMedCrossRef Bax DA, Gaspar N, Little SE, et al. EGFRvIII deletion mutations in pediatric high-grade glioma and response to targeted therapy in pediatric glioma cell lines. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2009;15(18):5753–61.PubMedCrossRef
68.
go back to reference Rood BR, MacDonald TJ. Pediatric high-grade glioma: molecular genetic clues for innovative therapeutic approaches. J Neurooncol. 2005;75(3):267–72.PubMedCrossRef Rood BR, MacDonald TJ. Pediatric high-grade glioma: molecular genetic clues for innovative therapeutic approaches. J Neurooncol. 2005;75(3):267–72.PubMedCrossRef
69.
go back to reference Thorarinsdottir HK, Santi M, McCarter R, et al. Protein expression of platelet-derived growth factor receptor correlates with malignant histology and PTEN with survival in childhood gliomas. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2008;14(11):3386–94.PubMedCrossRef Thorarinsdottir HK, Santi M, McCarter R, et al. Protein expression of platelet-derived growth factor receptor correlates with malignant histology and PTEN with survival in childhood gliomas. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2008;14(11):3386–94.PubMedCrossRef
70.
go back to reference Nakamura M, Shimada K, Ishida E, et al. Molecular pathogenesis of pediatric astrocytic tumors. Neuro Oncol. 2007;9(2):113–23.PubMedCrossRef Nakamura M, Shimada K, Ishida E, et al. Molecular pathogenesis of pediatric astrocytic tumors. Neuro Oncol. 2007;9(2):113–23.PubMedCrossRef
71.
go back to reference Broniscer A, Baker SJ, West AN, et al. Clinical and molecular characteristics of malignant transformation of low-grade glioma in children. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2007;25(6):682–9.PubMedCrossRef Broniscer A, Baker SJ, West AN, et al. Clinical and molecular characteristics of malignant transformation of low-grade glioma in children. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2007;25(6):682–9.PubMedCrossRef
72.
go back to reference Pollack IF, Hamilton RL, James CD, et al. Rarity of PTEN deletions and EGFR amplification in malignant gliomas of childhood: results from the Children’s Cancer Group 945 cohort. J Neurosurg. 2006;105(5 Suppl):418–24.PubMed Pollack IF, Hamilton RL, James CD, et al. Rarity of PTEN deletions and EGFR amplification in malignant gliomas of childhood: results from the Children’s Cancer Group 945 cohort. J Neurosurg. 2006;105(5 Suppl):418–24.PubMed
73.
go back to reference Paugh BS, Qu C, Jones C, et al. Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2010;28(18):3061–8.PubMedCrossRef Paugh BS, Qu C, Jones C, et al. Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2010;28(18):3061–8.PubMedCrossRef
74.
go back to reference Antonelli M, Buttarelli FR, Arcella A, et al. Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high-grade gliomas. J Neurooncol. 2010;99(2):209–15.PubMedCrossRef Antonelli M, Buttarelli FR, Arcella A, et al. Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high-grade gliomas. J Neurooncol. 2010;99(2):209–15.PubMedCrossRef
75.
go back to reference Fassan M, Tassone E, Onisto M, et al. MGMT promoter methylation in pediatric high-grade gliomas. Child's nervous system: ChNS: official journal of the International Society for Pediatric Neurosurgery. Childs Nerv Syst. 2011;27(1):7–8.PubMedCrossRef Fassan M, Tassone E, Onisto M, et al. MGMT promoter methylation in pediatric high-grade gliomas. Child's nervous system: ChNS: official journal of the International Society for Pediatric Neurosurgery. Childs Nerv Syst. 2011;27(1):7–8.PubMedCrossRef
76.
go back to reference Lee JY, Park CK, Park SH, et al. MGMT promoter gene methylation in pediatric glioblastoma: analysis using MS-MLPA. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 2011. Lee JY, Park CK, Park SH, et al. MGMT promoter gene methylation in pediatric glioblastoma: analysis using MS-MLPA. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 2011.
77.
go back to reference Gilbertson RJ, Hill DA, Hernan R, et al. ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2003;9(10 Pt 1):3620–4.PubMed Gilbertson RJ, Hill DA, Hernan R, et al. ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clinical cancer research: an official journal of the American Association for Cancer Research. Clin Cancer Res. 2003;9(10 Pt 1):3620–4.PubMed
78.
go back to reference Zarghooni M, Bartels U, Lee E, et al. Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2010;28(8):1337–44.PubMedCrossRef Zarghooni M, Bartels U, Lee E, et al. Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. J Clin Oncol. 2010;28(8):1337–44.PubMedCrossRef
79.
go back to reference Joshi BH, Puri RA, Leland P, et al. Identification of interleukin-13 receptor alpha2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma. Neuro Oncol. 2008;10(3):265–74.PubMedCrossRef Joshi BH, Puri RA, Leland P, et al. Identification of interleukin-13 receptor alpha2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma. Neuro Oncol. 2008;10(3):265–74.PubMedCrossRef
80.
go back to reference Barrow J, Adamowicz-Brice M, Cartmill M, et al. Homozygous loss of ADAM3A revealed by genome-wide analysis of pediatric high-grade glioma and diffuse intrinsic pontine gliomas. Neuro Oncol. 2011;13(2):212–22.PubMedCrossRef Barrow J, Adamowicz-Brice M, Cartmill M, et al. Homozygous loss of ADAM3A revealed by genome-wide analysis of pediatric high-grade glioma and diffuse intrinsic pontine gliomas. Neuro Oncol. 2011;13(2):212–22.PubMedCrossRef
81.
go back to reference Monje M, Mitra SS, Freret ME, et al. Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma. Proc Natl Acad Sci USA. 2011;108(11):4453–8.PubMedCrossRef Monje M, Mitra SS, Freret ME, et al. Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma. Proc Natl Acad Sci USA. 2011;108(11):4453–8.PubMedCrossRef
Metadata
Title
Impact of Molecular Biology Studies on the Understanding of Brain Tumors in Childhood
Authors
Amulya A. Nageswara Rao
Roger J. Packer
Publication date
01-04-2012
Publisher
Current Science Inc.
Published in
Current Oncology Reports / Issue 2/2012
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-012-0214-3

Other articles of this Issue 2/2012

Current Oncology Reports 2/2012 Go to the issue

Head and Neck Cancers (EY Hanna, Section Editor)

Current Progress in Adaptive Radiation Therapy for Head and Neck Cancer

Evolving Therapies (RM Bukowski, Section Editor)

RET TKI: Potential Role in Thyroid Cancers

Head and Neck Cancers (EY Hanna, Section Editor)

Salivary Gland Cancers: Biology and Molecular Targets for Therapy

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine