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Accueil Nota Bene Cancer V2 Numéro 127 du 13 March 2012 Biologie BREADCRUMB PUBLICATION

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A DNA hypermethylation module for the stem/progenitor cell signature of cancer

Menée sur différents types de cancer, cette étude identifie un "module d'hyperméthylation de l'ADN" comprenant un ensemble de gènes associés à une signature de cellule souche du cancer

  • Genome Research, sous presse, 2012 (article en libre accès)

Résumé en anglais :
Many DNA-hypermethylated cancer genes are occupied by the polycomb (PcG) repressor complex in embryonic stem cells (ESC). Their prevalence in the full spectrum of cancers, the exact context of chromatin involved, and their status in adult cell renewal systems are unknown. Using a genome-wide analysis, we demonstrate that approximately 75% of hypermethylated genes are marked by PcG in the context of bivalent chromatin in both ESC and adult stem/progenitor cells. A large number of these genes are key developmental regulators and a subset, which we call the "DNA hypermethylation module", comprise a portion of the PcG target genes that are downregulated in cancer. Genes with bivalent chromatin have a low, poised gene transcription state that has been shown to maintain stemness and self-renewal in normal stem cells. However, when DNA-hypermethylated in tumors, we find these genes are further repressed. We also show that the methylation status of these genes can cluster important subtypes of colon and breast cancers. By evaluating the subsets of genes that are methylated in different cancers with consideration of their chromatin status in ESCs, we provide evidence that DNA-hypermethylation preferentially targets the subset of PcG genes that are developmental regulators, and this may contribute to the stem-like state of cancer. Additionally, the capacity for global methylation profiling to cluster tumors by phenotype may have important implications for further refining tumor behavior patterns that may ultimately aid therapeutic interventions.

NBC n° 127 du 13 March 2012

Mots clés : Cancer (général); Biologie (Aberrations chromosomiques)

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