Tumour-specific distribution of BRCA1 promoter region methylation supportsa pathogenetic role in breast and ovarian cancer

The role of BRCA1 in sporadic breast and ovarian cancers remains elusive, D irect involvement of BRCA1 in the development of breast and ovarian cancer is suggested by the finding that the BRCA1 promoter region CpG island is me thylated in a proportion of breast and ovarian cancers. The aim of this stu dy was to compare the incidence of BRCA1 promoter region methylation in tum ours in which loss of BRCA1 has been shown to play a role in pathogenesis ( breast and ovarian carcinomas) with the incidence in tumours in which BRCA1 is unlikely to play a role in pathogenesis. Promoter region hypermethylati on was significantly more common (P < 0.008) in breast and ovarian cancer ( 6/38 tumours methylated) than in colon cancer (0/35 tumours methylated) or in leukaemias (0/19 samples methylated). The restriction of BRCA1 promoter region hypermethylation to breast and ovarian cancer is consistent with a p athogenetic role of BRCA1 promoter methylation in these tumours, We suggest that the rarity of observed BRCA1 mutations in sporadic breast and ovarian cancer is due to the greater likelihood of BRCA1 inactivation by non-mutat ional mechanisms such :ts methylation.