Miki Y, Swensen J, Shattuck-Eidens D, Futreal P A, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett L M, Ding W
Department of Medical Informatics, University of Utah Medical Center, Salt Lake City 84132.
Science. 1994 Oct 7;266(5182):66-71. doi: 10.1126/science.7545954.
A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a zinc finger domain in its amino-terminal region, but is otherwise unrelated to previously described proteins. Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology.
通过定位克隆方法，已鉴定出一个与17号染色体连锁的BRCA1基因的有力候选基因，该基因影响乳腺癌和卵巢癌的易感性。在八个推测分离BRCA1易感等位基因的家族中，有五个检测到可能的致病突变。这些突变包括一个11个碱基对的缺失、一个1个碱基对的插入、一个终止密码子、一个错义替代以及一个推断的调控突变。BRCA1基因在包括乳腺和卵巢在内的许多组织中表达，并编码一种预测的含1863个氨基酸的蛋白质。该蛋白质在其氨基末端区域含有一个锌指结构域，但在其他方面与先前描述的蛋白质无关。BRCA1的鉴定应有助于某些个体乳腺癌和卵巢癌易感性的早期诊断，以及更好地理解乳腺癌生物学。
