BRCA1

BRCA1 (Breast Cancer gene 1) encodes a 1863-amino acid nuclear protein that functions as a tumor suppressor through its role in DNA double-strand break repair, cell cycle checkpoint control, and transcriptional regulation. The protein contains a RING finger domain at the N-terminus and BRCT domains at the C-terminus, which are critical for its interactions with other DNA repair proteins like BRCA2, RAD51, and p53. Loss of BRCA1 function leads to genomic instability and increased susceptibility to malignant transformation. Germline mutations (over 1000 identified) follow an autosomal dominant inheritance pattern with incomplete penetrance. Beyond breast and ovarian cancers, BRCA1 mutations are associated with increased risks of fallopian tube, primary peritoneal, and prostate cancers. BRCA1-associated tumors are typically high-grade, triple-negative breast cancers (ER-, PR-, HER2-) and high-grade serous ovarian carcinomas. These cancers show sensitivity to PARP inhibitors due to synthetic lethality in the setting of homologous recombination deficiency. Genetic counseling and testing are recommended for individuals with strong family histories or Ashkenazi Jewish ancestry (founder mutations 185delAG and 5382insC).