Merajver S D, Pham T M, Caduff R F, Chen M, Poy E L, Cooney K A, Weber B L, Collins F S, Johnston C, Frank T S
Department of Internal Medicine, University of Michigan Medical School 48109, USA.
Nat Genet. 1995 Apr;9(4):439-43. doi: 10.1038/ng0495-439.
The BRCA1 gene on chromosome 17q21 is responsible for an autosomal dominant syndrome of increased susceptibility to breast and ovarian cancer but no somatic mutations in tumours have yet been described. To study the potential role of BRCA1 in sporadic carcinogenesis, we analysed the genomic DNA of tumour and normal fractions of 47 ovarian cancers for mutations in BRCA1 using the single-strand conformation polymorphism technique. We now describe somatic mutations in the DNA of four tumours which also had loss of heterozygosity (LOH) at a BRCA1 intragenic marker. Our data support a tumour suppressor mechanism for BRCA1; somatic mutations and LOH may result in inactivation of BRCA1 in at least a small number of ovarian cancers.
位于17号染色体q21区域的BRCA1基因与一种常染色体显性综合征相关，该综合征会增加患乳腺癌和卵巢癌的易感性，但尚未发现肿瘤中的体细胞突变。为了研究BRCA1在散发性致癌过程中的潜在作用，我们使用单链构象多态性技术分析了47例卵巢癌肿瘤组织和正常组织的基因组DNA中BRCA1基因的突变情况。我们现在描述了4例肿瘤DNA中的体细胞突变，这些肿瘤在BRCA1基因内标记处也存在杂合性缺失（LOH）。我们的数据支持BRCA1的肿瘤抑制机制；体细胞突变和LOH可能导致至少一小部分卵巢癌中的BRCA1失活。
