White blood cell BRCA1 promoter methylation status and ovarian cancer risk: A perspective
Menée en Norvège à partir des données d'une étude initiale incluant 934 patientes atteintes d'un cancer de l'ovaire et 1 698 témoins, puis validée sur 607 patientes et sur 1 984 témoins, cette étude évalue l'association entre la méthylation du promoteur du gène BRCA1 dans les globules blancs et le risque de développer la maladie
An increasing number of researchers consider changes in DNA methylation at the promoter regions of specific loci to be as important as genetic events in the initiation of cancer (1). The seminal publication that implicated promoter region methylation (hereafter referred to as methylation) as an initiating event in carcinogenesis was the report that methylation of a familial cancer driver, the RB1 tumor suppressor gene, was observed in nonfamilial retinoblastomas (2). Inactivation of the gene by epigenetic silencing, leading to functional loss of activity, thus was an alternative to mutational inactivation. It then became apparent that other genes that recurrently mutated in certain types of familial cancer, such as BRCA1, MLH1, and CDKN2A, could be methylated in the corresponding sporadic cancers. This finding indicated that inactivation of these genes by methylation might be the critical driver event in the development of those cases.