Bianco T, Chenevix-Trench G, Walsh D C, Cooper J E, Dobrovic A
Department of Haematology-Oncology, University of Adelaide, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia.
Carcinogenesis. 2000 Feb;21(2):147-51. doi: 10.1093/carcin/21.2.147.
The role of BRCA1 in sporadic breast and ovarian cancers remains elusive. Direct involvement of BRCA1 in the development of breast and ovarian cancer is suggested by the finding that the BRCA1 promoter region CpG island is methylated in a proportion of breast and ovarian cancers. The aim of this study was to compare the incidence of BRCA1 promoter region methylation in tumours 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 hypermethylation 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 pathogenetic 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-mutational mechanisms such as methylation.
BRCA1在散发性乳腺癌和卵巢癌中的作用仍不明确。BRCA1启动子区域CpG岛在一部分乳腺癌和卵巢癌中发生甲基化，这一发现提示BRCA1直接参与乳腺癌和卵巢癌的发生发展。本研究的目的是比较已证实BRCA1缺失在发病机制中起作用的肿瘤（乳腺癌和卵巢癌）中BRCA1启动子区域甲基化的发生率，与BRCA1不太可能在发病机制中起作用的肿瘤中该甲基化的发生率。启动子区域高甲基化在乳腺癌和卵巢癌（38例肿瘤中有6例甲基化）中比在结肠癌（35例肿瘤中0例甲基化）或白血病（19例样本中0例甲基化）中明显更常见（P < 0.008）。BRCA1启动子区域高甲基化仅限于乳腺癌和卵巢癌，这与BRCA1启动子甲基化在这些肿瘤中的致病作用一致。我们认为，散发性乳腺癌和卵巢癌中观察到的BRCA1突变罕见，是由于BRCA1通过甲基化等非突变机制失活的可能性更大。
