De Picciotto Nicolas, Cacheux Wulfran, Roth Arnaud, Chappuis Pierre O, Labidi-Galy S Intidhar
Center of Oncology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
Center of Oncology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland; Service of Genetic Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
Crit Rev Oncol Hematol. 2016 May;101:50-9. doi: 10.1016/j.critrevonc.2016.02.014. Epub 2016 Feb 27.
Epithelial ovarian cancer (EOC), particularly high-grade serous subtype, is associated with germline mutations in BRCA1/BRCA2 genes in up to 20% of the patients. BRCA1/BRCA2 proteins are important components of the homologous recombination (HR) pathway, a vital DNA repair process that protects the genome from double-strand DNA damage. Recent studies revealed frequent somatic mutations of BRCA1/BRCA2 and hypermethylation of the promoter of BRCA1 in EOC, in addition to germline mutations. Comparison of DNA copy number changes in tumors with or without BRCA1/BRCA2 alterations, lead to the identification of several signatures that detect HR pathway defects, here named "HRness". These signatures predict platinum-sensitivity and survival in EOC, as it was previously shown for germline mutations of BRCA1/BRCA2. They are currently investigated in clinical trials as potential predictive biomarker for response to poly(ADP- ribose) polymerase inhibitors.
上皮性卵巢癌（EOC），尤其是高级别浆液性亚型，在高达20%的患者中与BRCA1/BRCA2基因的种系突变相关。BRCA1/BRCA2蛋白是同源重组（HR）途径的重要组成部分，HR是一种重要的DNA修复过程，可保护基因组免受双链DNA损伤。最近的研究表明，除种系突变外，EOC中还频繁出现BRCA1/BRCA2的体细胞突变以及BRCA1启动子的高甲基化。比较有或没有BRCA1/BRCA2改变的肿瘤中的DNA拷贝数变化，导致鉴定出几种检测HR途径缺陷的特征，此处称为“HRness”。这些特征可预测EOC中的铂敏感性和生存率，正如之前针对BRCA1/BRCA2种系突变所显示的那样。它们目前正在临床试验中作为对聚（ADP - 核糖）聚合酶抑制剂反应的潜在预测生物标志物进行研究。
