Journal of Neuro-Oncology

, Volume 109, Issue 2, pp 415–423

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

  • 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
Clinical Study

DOI: 10.1007/s11060-012-0911-7

Cite this article as:
von Bueren, A.O., Gerss, J., Hagel, C. et al. J Neurooncol (2012) 109: 415. doi:10.1007/s11060-012-0911-7

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.

Keywords

Chromosomal imbalances Prognostic markers Comparative genomic hybridization Brain tumor 

Supplementary material

11060_2012_911_MOESM1_ESM.ppt (140 kb)
Supplementary material 1 (PPT 137 kb)
11060_2012_911_MOESM2_ESM.pdf (1 mb)
Supplementary material 2 (PDF 1048 kb)
11060_2012_911_MOESM3_ESM.pdf (337 kb)
Supplementary material 3 (PDF 337 kb)
11060_2012_911_MOESM4_ESM.doc (36 kb)
Supplementary material 4 (DOC 36 kb)
11060_2012_911_MOESM5_ESM.doc (38 kb)
Supplementary material 5 (DOC 38 kb)

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • André O. von Bueren
    • 1
    • 4
  • Joachim Gerss
    • 2
  • Christian Hagel
    • 3
  • Haoyang Cai
    • 4
  • Marc Remke
    • 5
    • 6
  • Martin Hasselblatt
    • 7
  • Burt G. Feuerstein
    • 8
  • Sarah Pernet
    • 9
  • Olivier Delattre
    • 9
  • Andrey Korshunov
    • 10
  • Stefan Rutkowski
    • 1
  • Stefan M. Pfister
    • 5
    • 6
  • Michael Baudis
    • 4
  1. 1.Department of Pediatric Hematology and OncologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.Institute of Biostatistics and Clinical ResearchUniversity of MuensterMuensterGermany
  3. 3.Institute of NeuropathologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  4. 4.Institute of Molecular Life SciencesUniversity of ZurichZurichSwitzerland
  5. 5.Division of Pediatric NeurooncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  6. 6.Department of Pediatric Hematology and OncologyHeidelberg University HospitalHeidelbergGermany
  7. 7.Institute of NeuropathologyUniversity of MuensterMuensterGermany
  8. 8.Department of Neurology, Barrow Neurological Institute—St. Joseph’s Hospital and Medical CenterUniversity of Arizona College of MedicinePhoenixUSA
  9. 9.Institut CurieUnité de génétique somatiqueParisFrance
  10. 10.Department of NeuropathologyUniversity of HeidelbergHeidelbergGermany

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