Top

Published in:

01-09-2012 | Clinical Study

DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis

Authors: André O. von Bueren, Joachim Gerss, Christian Hagel, Haoyang Cai, Marc Remke, Martin Hasselblatt, Burt G. Feuerstein, Sarah Pernet, Olivier Delattre, Andrey Korshunov, Stefan Rutkowski, Stefan M. Pfister, Michael Baudis

Published in: Journal of Neuro-Oncology | Issue 2/2012

Abstract

Little is known about frequency, association with clinical characteristics, and prognostic impact of DNA copy number alterations (CNA) on survival in central primitive neuroectodermal tumors (CNS-PNET) and tumors of the pineal region. Searches of MEDLINE, Pubmed, and EMBASE—after the original description of comparative genomic hybridization in 1992 and July 2010—identified 15 case series of patients with CNS-PNET and tumors of the pineal region whose tumors were investigated for genome-wide CNA. One additional case study was identified from contact with experts. Individual patient data were extracted from publications or obtained from investigators, and CNAs were converted to a digitized format suitable for data mining and subgroup identification. Summary profiles for genomic imbalances were generated from case-specific data. Overall survival (OS) was estimated using the Kaplan–Meier method, and by univariable and multivariable Cox regression models. In their overall CNA profiles, low grade tumors of the pineal region clearly diverged from CNS-PNET and pineoblastoma. At a median follow-up of 89 months, 7-year OS rates of CNS-PNET, pineoblastoma, and low grade tumors of the pineal region were 22.9 ± 6, 0 ± 0, and 87.5 ± 12 %, respectively. Multivariable analysis revealed that histology (CNS-PNET), age (≤2.5 years), and possibly recurrent CNAs were associated with unfavorable OS. DNA copy number profiling suggests a close relationship between CNS-PNET and pineoblastoma. Low grade tumors of the pineal region differed from CNS-PNET and pineoblastoma. Due to their high biological and clinical variability, a coordinated prospective validation in future studies is necessary to establish robust risk factors.

Available only for authorised users

Gaffney CC, Sloane JP, Bradley NJ, Bloom HJ (1985) Primitive neuroectodermal tumours of the cerebrum. Pathology and treatment. J Neurooncol 3:23–33PubMedCrossRef

Li M, Lee KF, Lu Y, Clarke I, Shih D, Eberhart C, Collins VP, Van Meter T, Picard D, Zhou L, Boutros PC, Modena P, Liang ML, Scherer SW, Bouffet E, Rutka JT, Pomeroy SL, Lau CC, Taylor MD, Gajjar A, Dirks PB, Hawkins CE, Huang A (2009) Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors. Cancer Cell 16:533–546PubMedCrossRef

Timmermann B, Kortmann RD, Kuhl J, Rutkowski S, Meisner C, Pietsch T, Deinlein F, Urban C, Warmuth-Metz M, Bamberg M (2006) Role of radiotherapy in supratentorial primitive neuroectodermal tumor in young children: results of the German HIT-SKK87 and HIT-SKK92 trials. J Clin Oncol 24:1554–1560PubMedCrossRef

Fangusaro J, Massimino M, Rutkowski S, Gururangan S (2010) Non-cerebellar primitive neuroectodermal tumors (PNET): summary of the Milan consensus and state of the art workshop on marrow ablative chemotherapy with hematopoietic cell rescue for malignant brain tumors of childhood and adolescents. Pediatr Blood Cancer 54:638–640PubMedCrossRef

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system. IARC, Lyon

Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951PubMedCrossRef

Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821PubMedCrossRef

Joos S, Bergerheim US, Pan Y, Matsuyama H, Bentz M, du Manoir S, Lichter P (1995) Mapping of chromosomal gains and losses in prostate cancer by comparative genomic hybridization. Genes Chromosom Cancer 14:267–276PubMedCrossRef

Solinas-Toldo S, Lampel S, Stilgenbauer S, Nickolenko J, Benner A, Dohner H, Cremer T, Lichter P (1997) Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosom Cancer 20:399–407PubMedCrossRef

10.

Pollack JR, Perou CM, Alizadeh AA, Eisen MB, Pergamenschikov A, Williams CF, Jeffrey SS, Botstein D, Brown PO (1999) Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nat Genet 23:41–46PubMedCrossRef

11.

Bown N, Cotterill S, Lastowska M, O’Neill S, Pearson AD, Plantaz D, Meddeb M, Danglot G, Brinkschmidt C, Christiansen H, Laureys G, Speleman F, Nicholson J, Bernheim A, Betts DR, Vandesompele J, Van Roy N (1999) Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma. N Engl J Med 340:1954–1961PubMedCrossRef

12.

Zenz T, Mertens D, Dohner H, Stilgenbauer S (2008) Molecular diagnostics in chronic lymphocytic leukemia—pathogenetic and clinical implications. Leuk Lymphoma 49:864–873PubMedCrossRef

13.

Moinzadeh P, Breuhahn K, Stutzer H, Schirmacher P (2005) Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade–results of an explorative CGH meta-analysis. Br J Cancer 92:935–941PubMedCrossRef

14.

Baudis M (2007) Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta-analysis of chromosomal CGH data. BMC Cancer 7:226PubMedCrossRef

15.

Russo C, Pellarin M, Tingby O, Bollen AW, Lamborn KR, Mohapatra G, Collins VP, Feuerstein BG (1999) Comparative genomic hybridization in patients with supratentorial and infratentorial primitive neuroectodermal tumors. Cancer 86:331–339PubMedCrossRef

16.

Pfister S, Remke M, Toedt G, Werft W, Benner A, Mendrzyk F, Wittmann A, Devens F, von Hoff K, Rutkowski S, Kulozik A, Radlwimmer B, Scheurlen W, Lichter P, Korshunov A (2007) Supratentorial primitive neuroectodermal tumors of the central nervous system frequently harbor deletions of the CDKN2A locus and other genomic aberrations distinct from medulloblastomas. Genes Chromosom Cancer 46:839–851PubMedCrossRef

17.

Miller S, Rogers HA, Lyon P, Rand V, Adamowicz-Brice M, Clifford SC, Hayden JT, Dyer S, Pfister S, Korshunov A, Brundler MA, Lowe J, Coyle B, Grundy RG (2011) Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma. Neuro Oncol 13:866–879PubMedCrossRef

18.

Clarke M, Godwin J (1998) Systematic reviews using individual patient data: a map for the minefields? Ann Oncol 9:827–833PubMedCrossRef

19.

Riley RD, Sauerbrei W, Altman DG (2009) Prognostic markers in cancer: the evolution of evidence from single studies to meta-analysis, and beyond. Br J Cancer 100:1219–1229PubMedCrossRef

20.

Altman DG (2001) Systematic reviews of evaluations of prognostic variables. BMJ 323:224–228PubMedCrossRef

21.

Baudis M, Cleary ML (2001) Progenetix.net: an online repository for molecular cytogenetic aberration data. Bioinformatics 17:1228–1229PubMedCrossRef

22.

Baudis M (2006) Online database and bioinformatics toolbox to support data mining in cancer cytogenetics. Biotechniques 40:269–270, 272

23.

Wilne S, Collier J, Kennedy C, Koller K, Grundy R, Walker D (2007) Presentation of childhood CNS tumours: a systematic review and meta-analysis. Lancet Oncol 8:685–695PubMedCrossRef

24.

Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097PubMedCrossRef

25.

Stewart LA, Tierney JF (2002) To IPD or not to IPD? Advantages and disadvantages of systematic reviews using individual patient data. Eval Health Prof 25:76–97PubMedCrossRef

26.

Simmonds MC, Higgins JP, Stewart LA, Tierney JF, Clarke MJ, Thompson SG (2005) Meta-analysis of individual patient data from randomized trials: a review of methods used in practice. Clin Trials 2:209–217PubMedCrossRef

27.

Boerma EG, Siebert R, Kluin PM, Baudis M (2009) Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of todays knowledge. Leukemia 23:225–234PubMedCrossRef

28.

LeBlanc M, Crowley J (1992) Relative risk trees for censored survival data. Biometrics 48:411–425PubMedCrossRef

29.

Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRef

30.

Kleihues P, Cavenee WK (2000) World Health Organization classification of tumours. Pathology and genetics of tumours of the nervous system. IARC, Lyon

31.

Eberhart CG, Brat DJ, Cohen KJ, Burger PC (2000) Pediatric neuroblastic brain tumors containing abundant neuropil and true rosettes. Pediatr Dev Pathol 3:346–352PubMedCrossRef

32.

Paulus W, Kleihues P (2010) Genetic profiling of CNS tumors extends histological classification. Acta Neuropathol 120:269–270PubMedCrossRef

33.

Korshunov A, Remke M, Gessi M, Ryzhova M, Hielscher T, Witt H, Tobias V, Buccoliero AM, Sardi I, Gardiman MP, Bonnin J, Scheithauer B, Kulozik AE, Witt O, Mork S, von Deimling A, Wiestler OD, Giangaspero F, Rosenblum M, Pietsch T, Lichter P, Pfister SM (2010) Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes. Acta Neuropathol 120:253–260PubMedCrossRef

34.

Schwalbe EC, Lindsey JC, Straughton D, Hogg TL, Cole M, Megahed H, Ryan SL, Lusher ME, Taylor MD, Gilbertson RJ, Ellison DW, Bailey S, Clifford SC (2011) Rapid diagnosis of medulloblastoma molecular subgroups. Clin Cancer Res 17:1883–1894PubMedCrossRef

35.

Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC, Chintagumpala M, Adesina A, Ashley DM, Kellie SJ, Taylor MD, Curran T, Gajjar A, Gilbertson RJ (2006) Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 24:1924–1931PubMedCrossRef

36.

Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsic A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3:e3088PubMedCrossRef

37.

Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, Berhoukim R, Amani V, Goumnerova L, Eberhart CG, Lau CC, Olson JM, Gilbertson RJ, Gajjar A, Delattre O, Kool M, Ligon K, Meyerson M, Mesirov JP, Pomeroy SL (2011) Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol 29:1424–1430PubMedCrossRef

38.

Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, Bouffet E, Clifford SC, Hawkins CE, French P, Rutka JT, Pfister S, Taylor MD (2011) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29:1408–1414PubMedCrossRef

39.

Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A, Benner A, von Deimling A, Scheurlen W, Perry A, Croul S, Kulozik AE, Lichter P, Taylor MD, Pfister SM, Korshunov A (2011) Adult medulloblastoma comprises three major molecular variants. J Clin Oncol 29:2717–2723PubMedCrossRef

40.

Remke M, Hielscher T, Korshunov A, Northcott PA, Bender S, Kool M, Westermann F, Benner A, Cin H, Ryzhova M, Sturm D, Witt H, Haag D, Toedt G, Wittmann A, Schottler A, von Bueren AO, von Deimling A, Rutkowski S, Scheurlen W, Kulozik AE, Taylor MD, Lichter P, Pfister SM (2011) FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma. J Clin Oncol 29:3852–3861PubMedCrossRef

41.

Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A, Ellison DW, Lichter P, Gilbertson RJ, Pomeroy SL, Kool M, Pfister SM (2012) Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123:465–472PubMedCrossRef

42.

Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA, Cho YJ, Koster J, Schouten-van Meeteren A, van Vuurden D, Clifford SC, Pietsch T, von Bueren AO, Rutkowski S, McCabe M, Collins VP, Backlund ML, Haberler C, Bourdeaut F, Delattre O, Doz F, Ellison DW, Gilbertson RJ, Pomeroy SL, Taylor MD, Lichter P, Pfister SM (2012) Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas. Acta Neuropathol 123:473–484PubMedCrossRef

43.

Geyer JR, Sposto R, Jennings M, Boyett JM, Axtell RA, Breiger D, Broxson E, Donahue B, Finlay JL, Goldwein JW, Heier LA, Johnson D, Mazewski C, Miller DC, Packer R, Puccetti D, Radcliffe J, Tao ML, Shiminski-Maher T (2005) Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol 23:7621–7631PubMedCrossRef

44.

Pizer BL, Weston CL, Robinson KJ, Ellison DW, Ironside J, Saran F, Lashford LS, Tait D, Lucraft H, Walker DA, Bailey CC, Taylor RE (2006) Analysis of patients with supratentorial primitive neuro-ectodermal tumours entered into the SIOP/UKCCSG PNET 3 study. Eur J Cancer 42:1120–1128PubMedCrossRef

45.

Timmermann B, Kortmann RD, Kuhl J, Meisner C, Dieckmann K, Pietsch T, Bamberg M (2002) Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. J Clin Oncol 20:842–849PubMedCrossRef

46.

Li MH, Bouffet E, Hawkins CE, Squire JA, Huang A (2005) Molecular genetics of supratentorial primitive neuroectodermal tumors and pineoblastoma. Neurosurg Focus 19:E3PubMed

Title: DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis
Authors: André O. von Bueren
Joachim Gerss
Christian Hagel
Haoyang Cai
Marc Remke
Martin Hasselblatt
Burt G. Feuerstein
Sarah Pernet
Olivier Delattre
Andrey Korshunov
Stefan Rutkowski
Stefan M. Pfister
Michael Baudis
Publication date: 01-09-2012
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2012
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-012-0911-7

At a glance: The STEP trials

Springer Medicine

DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2012

Identification of a novel population in high-grade oligodendroglial tumors not deleted on 1p/19q using array CGH

Primary tumor response to chemoradiotherapy in limited-disease small-cell lung cancer correlates with duration of brain-metastasis free survival

Leptomeningeal seeding in patients with brain metastases treated by gamma knife radiosurgery

Stereotactic iodine-125 brachytherapy for treatment of inoperable focal brainstem gliomas of WHO grades I and II: feasibility and long-term outcome

Intracavitary brachytherapy using stereotactically applied phosphorus-32 colloid for treatment of cystic craniopharyngiomas in 53 patients

E-cadherin as a predictive marker of brain metastasis in non-small-cell lung cancer, and its regulation by pioglitazone in a preclinical model