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
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 |