Evidence for an instructive mechanism of de novo methylation in cancer cells

Ilana Keshet*, Yeshayahu Schlesinger, Shlomit Farkash, Eyal Rand, Merav Hecht, Eran Segal, Eli Pikarski, Richard A. Young, Alain Niveleau, Howard Cedar, Itamar Simon

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

403 Scopus citations


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.

Original languageAmerican English
Pages (from-to)149-153
Number of pages5
JournalNature Genetics
Issue number2
StatePublished - Feb 2006

Bibliographical note

Funding Information:
Colon biopsies were provided by J. Zimmerman. We thank R. Rubinstein and M. Kott for help in the computer and microarray analyses. This research was supported by grants from the Rosetrees Trust, the US National Institutes of Health, the Israel Cancer Research Fund, the Belfer Foundation, the Conquer Fragile X Foundation, the Prostate Cancer Foundation, Fondation pour la Recherche Medicale-Ligue Nationale Francaise Contre le Cancer, Association for International Cancer Research (AICR) and the Bikura program of the Israel Science Foundation.


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