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Prediction
of central nervous system embryonal tumour outcome based on gene expression
Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim
JY, 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
Division of Neuroscience, Department of Neurology, Massachusetts
General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
scott.pomeroy@tch.harvard.edu
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.
PMID: 11807556 [PubMed - indexed for MEDLINE]
Source: http://theoncologist.alphamedpress.org/cgi/external_ref?access_num=11807556&link_type=MED
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