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 patients’ 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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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.

Author information


  1. *Division of Neuroscience, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Scott L. Pomeroy
    • , Lisa M. Sturla
    •  & John Y. H. Kim
  2. ‡Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Margaret E. McLaughlin
  3. Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Liliana C. Goumnerova
    •  & Peter M. Black
  4. Department of Medicine, Children's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Todd R. Golub
  5. §Department of Pediatric Oncology, Dana-Farber Cancer Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • John Y. H. Kim
    •  & Todd R. Golub
  6. ¶¶Department of Pathology and Neurosurgical Service, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • David N. Louis
  7. †Whitehead Institute/MIT Center for Genome Research, AI Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Pablo Tamayo
    • , Michelle Gaasenbeek
    • , Michael Angelo
    • , Jill P. Mesirov
    • , Eric S. Lander
    •  & Todd R. Golub
  8. §§McGovern Institute, Center for Biological and Computational Learning, AI Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Tomaso Poggio
    • , Shayan Mukherjee
    •  & Ryan Rifkin
  9. ¶Division of Pediatric Oncology, Baylor College of Medicine, Houston, Texas 77030, USA

    • Ching Lau
  10. #Beth Israel Medical Center, New York 10128, USA

    • Jeffrey C. Allen
  11. Department of Pathology, New York University School of Medicine, New York 10016, USA

    • David Zagzag
  12. **Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA

    • James M. Olson
  13. ††Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA

    • Tom Curran
    •  & Cynthia Wetmore
  14. ‡‡Division of Human Genetics, The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA

    • Jaclyn A. Biegel
  15. ##Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Eric S. Lander
  16. IBM Watson Research Center, Yorktown Heights, New York 10598, USA

    • Andrea Califano
    •  & Gustavo Stolovitzky


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Competing interests

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.

Corresponding authors

Correspondence to Scott L. Pomeroy or Todd R. Golub.

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