T. Bianco et al., Tumour-specific distribution of BRCA1 promoter region methylation supportsa pathogenetic role in breast and ovarian cancer, CARCINOGENE, 21(2), 2000, pp. 147-151
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.