BRCA2
小结
BRCA2是抑癌基因，编码蛋白起着DNA修复蛋白的作用，在各种癌症类型中均会发生突变。BRCA2涉及调节多种细胞过程，包括转录，细胞周期调节和DNA损伤反应；在同源重组过程中的DNA修复中具有特别重要的作用。BRCA2常与已知的肿瘤抑制因子形成蛋白质复合物发挥作用，包括RAD51，BRCA1和PALB2；具体而言，BRCA2结合单链DNA并在DNA双链断裂位点加载RAD51D单体。RAD51需要BRCA1-BRCA2-PALB2复合物来启动同源重组。BRCA2胚系杂合致病突变可导致遗传性乳腺-卵巢综合征，因为该综合征是常染色体显性遗传病。同时，BRCA2也时Fanconi贫血易感基因，需要BRCA2发生双等位基因突变才会患病，因为Fanconi贫血属于一种常染色体隐形遗传病。胚系BRCA2突变导致30-60％的终生乳腺癌风险，30％的卵巢癌终生风险，20％的前列腺癌风险以及发生多种癌症的风险。乳腺肿瘤中TP53的突变几乎全部见于BRCA1和BRCA2突变，表明TP53功能丧失可能是BRCA相关癌的肿瘤发生的必要步骤。
BRCA2 (breast cancer susceptibility gene 2) is a tumor suppressor gene that functions as a DNA repair protein. BRCA2 has been implicated in regulating diverse cellular processes including transcription, cell cycle regulation, and DNA damage response, with a particularly important role in DNA repair during homologous recombination. BRCA2 forms protein complexes with known tumor suppressors including RAD51, BRCA1, and PALB2; specifically, BRCA2 binds single-stranded DNA and loads RAD51 monomers at sites of DNA double-strand breaks. RAD51 requires the BRCA1-BRCA2-PALB2 complex to initiate homologous recombination. BRCA2 is a tumor suppressor protein; if one copy of the gene is inactivated in the germ line, the result is hereditary breast and ovarian cancer (HBOC) syndrome, an autosomal dominant disease. BRCA2 was also identified as a definitive Fanconi anemia susceptibility gene that results from biallelic mutations in the gene. Germline BRCA2 mutations confer a 50-60% lifetime risk of breast cancer, a 30% lifetime risk of ovarian cancer, a 20-fold increased risk of prostate cancer, and a risk for the development of a broad range of cancers. Mutations in TP53 in breast tumors are seen almost exclusively with BRCA1 and BRCA2 mutations, suggesting that TP53 loss of function may be a necessary step in the tumorigenesis of BRCA-associated carcinomas. PARP inhibitors are FDA-approved for patients with germline BRCA2-mutant ovarian and breast cancers.