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

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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.

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Acknowledgments

The authors’ are indebted to the authors of articles, who provided the data to this study that otherwise would not have been accessible. In particular, the authors would like to thank the following researcher/clinicians for their help: Milo Puhan, Carolyn Russo, Wolfram Scheurlen, Barbara Schütz, Christine Haberler, Martin McCabe, and Hans-Hermann Dubben. The author would like to thank Klaus-Dieter Papke for assisting the literature search. The authors acknowledge the following sources of funding: German Children‘s Cancer Foundation/Deutsche Kinderkrebsstiftung (to A.O.V.B., S.R.). Haoyang Cai is supported through a grant from the China Scholarship Council.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    André O. von Bueren & Stefan Rutkowski

  2. Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany

    Joachim Gerss

  3. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Christian Hagel

  4. Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland

    André O. von Bueren, Haoyang Cai & Michael Baudis

  5. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Marc Remke & Stefan M. Pfister

  6. Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Marc Remke & Stefan M. Pfister

  7. Institute of Neuropathology, University of Muenster, Muenster, Germany

    Martin Hasselblatt

  8. Department of Neurology, Barrow Neurological Institute—St. Joseph’s Hospital and Medical Center, University of Arizona College of Medicine, Phoenix, AZ, USA

    Burt G. Feuerstein

  9. Institut Curie, Unité de génétique somatique, Paris, France

    Sarah Pernet & Olivier Delattre

  10. Department of Neuropathology, University of Heidelberg, Heidelberg, Germany

    Andrey Korshunov

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  1. André O. von Bueren
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Correspondence to André O. von Bueren.

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von Bueren, A.O., Gerss, J., Hagel, C. et al. DNA copy number alterations in central primitive neuroectodermal tumors and tumors of the pineal region: an international individual patient data meta-analysis. J Neurooncol 109, 415–423 (2012). https://doi.org/10.1007/s11060-012-0911-7

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