Evidence for an instructive mechanism of de novo methylation in cancer cells.
DNA methylation has a role in the regulation of gene expression during normal mammalian development but can also mediate epigenetic silencing of CpG island genes in cancer and other diseases. Many individual genes (including tumor suppressors) have been shown to undergo de novo methylation in specific tumor types, but the biological logic inherent in this process is not understood. To decipher this mechanism, we have adopted a new approach for detecting CpG island DNA methylation that can be used together with microarray technology. Genome-wide analysis by this technique demonstrated that tumor-specific methylated genes belong to distinct functional categories, have common sequence motifs in their promoters and are found in clusters on chromosomes. In addition, many are already repressed in normal cells. These results are consistent with the hypothesis that cancer-related de novo methylation may come about through an instructive mechanism.
Keshet
Ilana
I
Department of Cellular Biochemistry and Human Genetics, Hebrew University, Jerusalem, Israel.
Schlesinger
Yeshayahu
Y
Farkash
Shlomit
S
Rand
Eyal
E
Hecht
Merav
M
Segal
Eran
E
Pikarski
Eli
E
Young
Richard A
RA
Niveleau
Alain
A
Cedar
Howard
H
Simon
Itamar
I
D000818:Animals; D002875:Chromosomes / Q000235:genetics; D019295:Computational Biology; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology