CONFIRMATION OF BRCA1 LAY ANALYSIS OF GERMLINE MUTATIONS LINKED TO BREAST AND OVARIAN-CANCER IN 10 FAMILIES
CONFIRMATION OF BRCA1 LAY ANALYSIS OF GERMLINE MUTATIONS LINKED TO BREAST AND OVARIAN-CANCER IN 10 FAMILIES
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DOI：
10.1038/ng1294-399
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发表时间：
1994-12-01
期刊：
影响因子：
30.8
通讯作者：
KING, MC
中科院分区：
文献类型：
--
作者：
FRIEDMAN, LS;OSTERMEYER, EA;KING, MC
我们通过对10个与染色体17 g21相关的癌症家族中63名乳腺癌患者和10名卵巢癌患者的生殖系突变进行表征，提供了支持BRCA 1候选基因身份的遗传学证据。采用单链构象多态性分析和直接测序技术对BRCA 1基因进行DNA和RNA筛查，共检测到9种不同的突变。七个突变导致蛋白质截短的网站在整个基因。一个错义突变（在两个家族中独立发生）导致锌结合结构域中的半胱氨酸丢失。内含子单碱基对取代破坏受体位点并激活隐蔽剪接位点，导致59个碱基对插入和链终止。这四个同时患有乳腺癌和卵巢癌的家族在蛋白质的N-末端的一半有链终止突变。
We provide genetic evidence supporting the identity of the candidate gene for BRCA1 through the characterization of germline mutations in 63 breast cancer patients and 10 ovarian cancer patients in ten families with cancer linked to chromosome 17g21. Nine different mutations were detected by screening BRCA1 DNA and RNA by single-strand conformation polymorphism analysis and direct sequencing. Seven mutations lead to protein truncations at sites throughout the gene. One missense mutation (which occurred independently in two families) leads to loss of a cysteine in the zinc binding domain. An intronic single basepair substitution destroys an acceptor site and activates a cryptic splice site, leading to a 59 basepair insertion and chain termination. The four families with both breast and ovarian cancer had chain termination mutations in the N-terminal half of the protein.