Ingvarsson S
Department of Pathology, University Hospital of Iceland, Reykjavik, Iceland.
Anticancer Res. 1999 Jul-Aug;19(4B):2853-61.
Germline alterations of the BRCA1 or BRCA2 genes result in susceptibility to breast and ovarian cancer. Protein-protein interaction studies, transcription activity and mouse knockout experiments have suggested that the Brca1 and Brca2 proteins are of importance in DNA repair and maintenance of genome integrity, possibly due to the transactivation function of Brca1 or Brca2. Subsequently, tumors in individuals carrying germline mutation in either BRCA1 or BRCA2 gene show instability at chromosomal and gene level. Chromosomal and gene alterations are more pronounced in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic tumors. Furthermore, BRCA1 and BRCA2 mutated breast tumors differ from sporadic tumors in respect to histological phenotype. Typically, a higher grade of malignancy is observed in familial tumors. This review summarizes the putative functions of the Brca1 and Brca2 proteins and pathogenesis in tumors of BRCA1 and BRCA2 mutation carriers.
BRCA1或BRCA2基因的种系改变会导致患乳腺癌和卵巢癌的易感性。蛋白质-蛋白质相互作用研究、转录活性及小鼠基因敲除实验表明，Brca1和Brca2蛋白在DNA修复和基因组完整性维持中具有重要作用，这可能归因于Brca1或Brca2的反式激活功能。随后，携带BRCA1或BRCA2基因种系突变的个体所患肿瘤在染色体和基因水平表现出不稳定性。与散发性肿瘤相比，BRCA1和BRCA2突变携带者的肿瘤中染色体和基因改变更为明显。此外，BRCA1和BRCA2突变的乳腺肿瘤在组织学表型方面与散发性肿瘤不同。通常，家族性肿瘤的恶性程度更高。本综述总结了Brca1和Brca2蛋白的假定功能以及BRCA1和BRCA2突变携带者肿瘤的发病机制。
