Biallelic inactivation of BRCA2 in Fanconi anemia
Biallelic inactivation of BRCA2 in Fanconi anemia
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DOI：
10.1126/science.1073834
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发表时间：
2002-07-26
期刊：
影响因子：
56.9
通讯作者：
D'Andrea, AD
中科院分区：
文献类型：
--
作者：
Howlett, NG;Taniguchi, T;D'Andrea, AD
范可尼贫血(FA)是一种罕见的常染色体隐性遗传性癌症易感性疾病，其特征是细胞对丝裂霉素C(MMC)过敏。已克隆了6个FA基因，但与FA亚型B和D_1对应的一个或多个基因尚未确定。在这里，我们表明，来自FA-B和FA-D1患者的细胞系在BRCA2基因上存在双等位基因突变，并表达截短的BRCA2蛋白。FA-D1成纤维细胞与野生型BRCA2互补DNA的功能互补可恢复MMC抵抗。我们的结果将6个克隆的FA基因与BRCA1和BRCA2以一个共同的途径联系在一起。这一途径中基因的胚系突变可能会导致癌症风险，与在BRCA1或BRCA2突变家族中观察到的风险相似。
Fanconi anemia ( FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with wild-type BRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA1 or BRCA2 mutations.