原发性乳腺癌和卵巢癌中的BRCA2基因突变。

BRCA2 mutations in primary breast and ovarian cancers.

作者信息

Lancaster J M, Wooster R, Mangion J, Phelan C M, Cochran C, Gumbs C, Seal S, Barfoot R, Collins N, Bignell G, Patel S, Hamoudi R, Larsson C, Wiseman R W, Berchuck A, Iglehart J D, Marks J R, Ashworth A, Stratton M R, Futreal P A

机构信息

Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.

出版信息

Nat Genet. 1996 Jun;13(2):238-40. doi: 10.1038/ng0696-238.

DOI:10.1038/ng0696-238

PMID:8640235

Abstract

The second hereditary breast cancer gene, BRCA2, was recently isolated. Germline mutations of this gene predispose carriers to breast cancer, and, to a lesser extent, ovarian cancer. Loss of heterozygosity (LOH) at the BRCA2 locus has been observed in 30-40% of sporadic breast and ovarian tumours, implying that BRCA2 may act as a tumour suppressor gene in a proportion of sporadic cases. To define the role of BRCA2 in sporadic breast and ovarian cancer, we screened the entire gene for mutations using a combination of techniques in 70 primary breast carcinomas and in 55 primary epithelial ovarian carcinomas. Our analysis revealed alterations in 2/70 breast tumours and none of the ovarian carcinomas. One alteration found in the breast cancers was a 2-basepair (bp) deletion (4710delAG) which was subsequently shown to be a germline mutation, the other was a somatic missense mutation (Asp3095Glu) of unknown significance. Our results suggest that BRCA2 is a very infrequent target for somatic inactivation in breast and ovarian carcinomas, similar to the results obtained for BRCA1.

摘要

第二个遗传性乳腺癌基因BRCA2最近被分离出来。该基因的种系突变使携带者易患乳腺癌，在较小程度上也易患卵巢癌。在30%至40%的散发性乳腺癌和卵巢肿瘤中观察到BRCA2基因座的杂合性缺失（LOH），这意味着BRCA2在一部分散发性病例中可能作为肿瘤抑制基因发挥作用。为了确定BRCA2在散发性乳腺癌和卵巢癌中的作用，我们使用多种技术对70例原发性乳腺癌和55例原发性上皮性卵巢癌的整个基因进行了突变筛查。我们的分析发现，70例乳腺癌中有2例发生改变，而卵巢癌中无一例发生改变。在乳腺癌中发现的一个改变是2个碱基对（bp）的缺失（4710delAG），随后被证明是种系突变，另一个是意义不明的体细胞错义突变（Asp3095Glu）。我们的结果表明，与BRCA1的结果相似，BRCA2在乳腺癌和卵巢癌中是体细胞失活的非常罕见的靶点。