title: Prediction of central nervous system embryonal tumour outcome based on gene expression.
abstract: 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.
authors.affiliation: Division of Neuroscience, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. scott.pomeroy@tch.harvard.edu
authors.forename: Scott L
authors.initials: SL
authors.lastname: Pomeroy
authors.forename: Pablo
authors.initials: P
authors.lastname: Tamayo
authors.forename: Michelle
authors.initials: M
authors.lastname: Gaasenbeek
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sturla
authors.forename: Michael
authors.initials: M
authors.lastname: Angelo
authors.forename: Margaret E
authors.initials: ME
authors.lastname: McLaughlin
authors.forename: John Y H
authors.initials: JY
authors.lastname: Kim
authors.forename: Liliana C
authors.initials: LC
authors.lastname: Goumnerova
authors.forename: Peter M
authors.initials: PM
authors.lastname: Black
authors.forename: Ching
authors.initials: C
authors.lastname: Lau
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Allen
authors.forename: David
authors.initials: D
authors.lastname: Zagzag
authors.forename: James M
authors.initials: JM
authors.lastname: Olson
authors.forename: Tom
authors.initials: T
authors.lastname: Curran
authors.forename: Cynthia
authors.initials: C
authors.lastname: Wetmore
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
authors.forename: Tomaso
authors.initials: T
authors.lastname: Poggio
authors.forename: Shayan
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Ryan
authors.initials: R
authors.lastname: Rifkin
authors.forename: Andrea
authors.initials: A
authors.lastname: Califano
authors.forename: Gustavo
authors.initials: G
authors.lastname: Stolovitzky
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Jill P
authors.initials: JP
authors.lastname: Mesirov
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
mesh_terms: 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