Department of Pathology and Cell Biology, University of South Florida, Tampa, FL 33612, USA.
FEBS J. 2010 Aug;277(15):3086-96. doi: 10.1111/j.1742-4658.2010.07735.x. Epub 2010 Jul 1.
Mutations in the tumor suppressor breast cancer susceptibility gene 1 (BRCA1), an important player in the DNA damage response, apoptosis, cell cycle regulation and transcription, confer a significantly elevated lifetime risk for breast and ovarian cancer. Although the loss of wild-type BRCA1 function is an important mechanism by which mutations confer increased cancer risk, multiple studies suggest mutant BRCA1 proteins may confer functions independent of the loss of wild-type BRCA1 through dominant negative inhibition of remaining wild-type BRCA1, or through novel interactions and pathways. These functions impact various cellular processes and have the potential to significantly influence cancer initiation and progression. In this review, we discuss the functional classifications of risk-associated BRCA1 mutations and their molecular, cellular and clinical impact for mutation carriers.
肿瘤抑制基因 1（BRCA1）的突变，该基因在 DNA 损伤反应、细胞凋亡、细胞周期调控和转录中起重要作用，使乳腺癌和卵巢癌的终身风险显著增加。尽管野生型 BRCA1 功能的丧失是突变导致癌症风险增加的重要机制，但多项研究表明，突变 BRCA1 蛋白可能通过对剩余野生型 BRCA1 的显性负抑制，或通过新的相互作用和途径，赋予独立于野生型 BRCA1 丧失的功能。这些功能影响各种细胞过程，并有可能显著影响癌症的发生和发展。在这篇综述中，我们讨论了与风险相关的 BRCA1 突变的功能分类及其对突变携带者的分子、细胞和临床影响。
