Prediction of central nervous system embryonal tumour outcome based on gene expression.


Journal Article

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 debated, and patients' response to therapy is difficult to predict. 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.

Full Text

Cited Authors

  • Pomeroy, SL; Tamayo, P; Gaasenbeek, M; Sturla, LM; Angelo, M; McLaughlin, ME; Kim, JYH; Goumnerova, LC; Black, PM; Lau, C; Allen, JC; Zagzag, D; Olson, JM; Curran, T; Wetmore, C; Biegel, JA; Poggio, T; Mukherjee, S; Rifkin, R; Califano, A; Stolovitzky, G; Louis, DN; Mesirov, JP; Lander, ES; Golub, TR

Published Date

  • January 2002

Published In

Volume / Issue

  • 415 / 6870

Start / End Page

  • 436 - 442

PubMed ID

  • 11807556

Pubmed Central ID

  • 11807556

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/415436a


  • eng