Transcriptional profiling of medulloblastoma in children.
OBJECTIVE
Although medulloblastoma is the most common malignant brain tumor found in children, little is known about its molecular pathogenesis. The authors have attempted to compare patterns of gene expression in medulloblastoma samples with those in the healthy cerebellum.


METHODS
The authors used complementary (c)DNA microarray analysis to compare the expression of genes in samples of medulloblastoma and normal cerebellum. The expression levels of a subset of genes were then verified by immunohistochemical analysis. Six genes were identified that were expressed at a much higher level in at least five of six medulloblastomas: ezrin, cyclin D2, high mobility group protein 2, MAPRE1, histone deacetylase 2, and ornithine decarboxylase 1. A number of potentially important genes whose expression was much lower in medulloblastomas than in control cerebellum were also identified: tenascin R, TRK-B, FGF receptor, and death receptor 3. The expression levels of a subset of the identified genes were confirmed by immunohistochemical analysis, which was performed on fetal cerebellum and medulloblastoma samples.


CONCLUSIONS
The authors demonstrate that cDNA microarray analysis is an effective method of increasing understanding of the molecular biology of medulloblastomas found in children. A comparison between gene expression patterns in medulloblastoma and those observed in healthy cerebellum may provide clues as to the origin of these tumors and may lead to the identification of new genes or pathways to be targeted for future therapies.
Park
Paul C
PC
Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Taylor
Michael D
MD
Mainprize
Todd G
TG
Becker
Laurence E
LE
Ho
Michael
M
Dura
Wieslaw T
WT
Squire
Jeremy
J
Rutka
James T
JT
D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis