MUTATIONS IN THE BRCA1 GENE IN FAMILIES WITH EARLY-ONSET BREAST AND OVARIAN-CANCER
MUTATIONS IN THE BRCA1 GENE IN FAMILIES WITH EARLY-ONSET BREAST AND OVARIAN-CANCER
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DOI：
10.1038/ng1294-387
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发表时间：
1994-12-01
期刊：
影响因子：
30.8
通讯作者：
WEBER, BL
中科院分区：
文献类型：
--
作者：
CASTILLA, LH;COUCH, FJ;WEBER, BL
我们分析了50个有乳腺癌和/或卵巢癌家族史的先证者的BRCA1候选基因编码区的种系突变，使用PCR扩增的基因组DNA的单链构象多态性（SSCP）分析。总共鉴定了8个假定的致病改变：其中4个是移码，2个是无义突变。此外，我们还发现了两个错义突变，其中之一将BRCA1锌指基序的最后半胱氨酸改变为甘氨酸。这些数据与肿瘤抑制模型一致，并支持该候选基因实际上是BRCA1的观点。突变的异质性，加上基因的大尺寸，表明BRCA1突变检测的临床应用将在技术上具有挑战性。
We analysed 50 probands with a family history of breast and/or ovarian cancer for germline mutations in the coding region of the BRCA1 candidate gene, using single-strand conformation polymorphism (SSCP) analysis on PCR-amplified genomic DNA. A total Of eight putative disease-causing alterations were identified: four of these are frameshifts and two are nonsense mutations. In addition, we found two missense mutations, one of which changes the final cysteine of the BRCA1 zinc finger motif to glycine. These data are consistent with a tumour suppressor model, and support the notion that this candidate gene is in fact BRCA1. The heterogeneity of mutations, coupled with the large size of the gene, indicates that clinical application of BRCA1 mutation testing will be technically challenging.