Abstract
Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated1,2, and patientsâ response to therapy is difficult to predict3. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.
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Acknowledgements
We thank members of the Whitehead/MIT Center for Genome Research, Program in Cancer Genomics, and J. Volpe for discussions and comments on the manuscript. This work was supported in part by Millennium Pharmaceuticals, Affymetrix and Bristol-Myers Squibb (E.S.L.); NIH grants (S.L.P. and T.C.); NIH-supported Mental Retardation Research Center (S.L.P.) and Cancer Center Support CORE (T.C.); the American Lebanese Syrian Associated Charities (ALSAC); and the Kyle Mullarkey Medulloblastoma Research Fund. We acknowledge the Cooperative Human Tissue Network and the Children's Oncology Group for contributing tumour samples.
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We received research funding from Affymetrix (manufacturer of the microarrays used in this study) but do not have a financial (ownership) interest in the company.
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Pomeroy, S., Tamayo, P., Gaasenbeek, M. et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415, 436â442 (2002). https://doi.org/10.1038/415436a
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DOI: https://doi.org/10.1038/415436a
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