A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1

作者：Yoshio Miki, Jeffrey J. Swensen, Donna M. Shattuck-Eidens, P. Andrew Futreal, Keith Harshman, Sean V. Tavtigian, Qingyun Liu, Charles Cochran, L. Michelle Bennett, Wei Ding, Russell N. Bell, Judith Rosenthal, Charles E. Hussey, Thanh V. Tran, Melody McClure, Cheryl Anne Frye, Tom Hattier, Robert Phelps, Astrid C. Haugen, Harold L. Katcher, Kazuko Yakumo, Zahra Gholami, Daniel J. Shaffer, Steven Stone, Steven R Bayer, Christian Wray, Robert Bogden, Priya Dayananth, John Headley Ward, Patricia N. Tonin, Steven Alexander Narod, Pamela K. Bristow, Frank H. Norris, Leah M. Helvering, P. Morrison, Paul R. Rosteck, Mei Lai, J. Carl Barrett, Cathryn M. Lewis, Susan L. Neuhausen, Lisa Cannon‐Albright, David E. Goldgar, Roger W. Wiseman, Alexander Kamb, Mark H. Skolnick · 发表于：Science · 年份：1994 · DOI：10.1126/science.7545954 · 被引用次数：6133 · 研究领域：BRCA gene mutations in cancer、CRISPR and Genetic Engineering、DNA Repair Mechanisms

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.