title: DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis.
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.
authors: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. a.von-bueren@uke.de
authors: André O
authors: AO
authors: von Bueren
authors: Joachim
authors: J
authors: Gerss
authors: Christian
authors: C
authors: Hagel
authors: Haoyang
authors: H
authors: Cai
authors: Marc
authors: M
authors: Remke
authors: Martin
authors: M
authors: Hasselblatt
authors: Burt G
authors: BG
authors: Feuerstein
authors: Sarah
authors: S
authors: Pernet
authors: Olivier
authors: O
authors: Delattre
authors: Andrey
authors: A
authors: Korshunov
authors: Stefan
authors: S
authors: Rutkowski
authors: Stefan M
authors: SM
authors: Pfister
authors: Michael
authors: M
authors: Baudis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007223:Infant; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics*; D010870:Pineal Gland / Q000473:pathology*; D010871:Pinealoma / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult