Gene Expression-Based Classification and Outcome Prediction of Central Nervous System Embryonal Tumors

Nature, Vol 415, 24. Published: 2002.01.23

Scott L. Pomeroy, Pablo Tamayo, Michelle Gaasenbeek, Lisa M. Sturla, Michael Angelo, Margaret E. McLaughlin, John Y.H. Kim, Liliana C. Goumnerova, Peter McL. Black, Ching Lau, Jeffrey C. Allen, David Zagzag, James M.Olson, Tom Curran, Cynthia Wetmore, Jaclyn A. Biegel, Tomaso Poggio, Shayan Mukherjee, Ryan Rifkin, Andrea Califano, Gustavo Stolovitzky, David N. Louis, Jill P. Mesirov, Eric S. Lander and Todd R. Golub

Abstract

Embryonal tumors of the central nervous system (CNS) represent a heterogeneous group of tumors about which little is known biologically, and whose diagnosis, based on morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumor of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumors 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. We demonstrate that medulloblastomas are molecularly distinct from other brain tumors including primitive neuroectodermal tumors (PNET), atypical teratoid/rhabdoid tumors (AT/RT) 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 further show that the clinical outcome of children with medulloblastomas is highly predictable based on the gene expression profiles of their tumors at diagnosis.

Keywords: CNS tumors, medulloblastoma, malignant glioma, rhabdoid, PNET, Cancer Classification

Pca

Supplemental Data

Description Link/Filename
Manuscript (PDF) Brain_Nature.pdf
Supplementary Information document (MS Word) Pomeroy_et_al_0G04850_11142001_suppl_info.doc
Figures (MS Power Point) Pomeroy_et_al_0G04850_11142001_figures.ppt
Datasets and clinical table (ZIP, 13 Mbytes) Pomeroy_et_al_0G04850_11142001_datasets.zip
Sample list CNS_samples_CEL_files_list.xls
Raw data 1/4 (57 MB) scans_pt1.tar.gz
Raw data 2/4 (57 MB) scans_pt2.tar.gz
Raw data 3/4 (58 MB) scans_pt3.tar.gz
Raw data 4/4 (58 MB) scans_pt4.tar.gz
Dataset C (gene expression) RES file format Dataset_C_MD_outcome.res
Dataset C (class labels) CLS file format Dataset_C_MD_outcome.cls
Dataset C (clinical table) ASCII file format Brain_4_MD_outcome_2.survival.tex