Prediction of central nervous system embryonal tumour outcome based on gene expression.
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.
Pomeroy
Scott L
SL
Division of Neuroscience, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. scott.pomeroy@tch.harvard.edu
Tamayo
Pablo
P
Gaasenbeek
Michelle
M
Sturla
Lisa M
LM
Angelo
Michael
M
McLaughlin
Margaret E
ME
Kim
John Y H
JY
Goumnerova
Liliana C
LC
Black
Peter M
PM
Lau
Ching
C
Allen
Jeffrey C
JC
Zagzag
David
D
Olson
James M
JM
Curran
Tom
T
Wetmore
Cynthia
C
Biegel
Jaclyn A
JA
Poggio
Tomaso
T
Mukherjee
Shayan
S
Rifkin
Ryan
R
Califano
Andrea
A
Stolovitzky
Gustavo
G
Louis
David N
DN
Mesirov
Jill P
JP
Lander
Eric S
ES
Golub
Todd R
TR
D000293:Adolescent; D002528:Cerebellar Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D006801:Humans; D008527:Medulloblastoma / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017063:Outcome Assessment, Health Care; D011379:Prognosis