tailieunhanh - Báo cáo khoa học: BRCA1 16 years later: risk-associated BRCA1 mutations and their functional implications

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 life-time risk for breast and ovarian cancer. | ễFEBS Journal MINIREVIEW BRCA1 16 years later risk-associated BRCA1 mutations and their functional implications Rebecca J. Linger1 and Patricia A. Kruk1 2 1 Department of Pathology and CellBiology University of South Florida Tampa FL USA 2 H. Lee Moffitt Cancer Center Tampa FL USA Keywords BRCA1 breast cancer mutation ovarian cancer risk Correspondence P. A. Kruk Department of Pathology and CellBiology MDC 11 University of South Florida 12901 Bruce B. Downs Blvd Tampa FL 33612 USA Fax 813 974 5536 Tel 813 974 0548 E-mail pkruk@ Received 26 January 2010 revised 27 April 2010 accepted 4 June 2010 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. doi Introduction Family history is the strongest risk factor for the development of ovarian cancer and a major risk factor for the development of breast cancer 1 . Understanding how risk-associated mutations contribute to cancer initiation and progression will provide insight into molecular mechanisms and aid in better risk assessment prophylaxis and treatment for carriers. The majority of hereditary ovarian cancers and a significant proportion of .