Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France.
Clin Cancer Res. 2018 Jan 15;24(2):326-333. doi: 10.1158/1078-0432.CCR-17-2136. Epub 2017 Oct 30.
BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of gene affects the clinical outcome of ovarian cancer patients. A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for and genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer ( = 316) was used as a validation cohort. In the study cohort, 78 patients were carriers of germline mutations of After adjustment for FIGO stage and macroscopic residual disease, carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS [58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20-0.64; = 0.001] and prolonged PFI (29.7 vs. 15.5 months, = 0.011), compared with noncarriers. carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42-1.07; = 0.094) or PFI (19 vs. 15.5 months, = 0.146). In the TCGA cohort, only carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13-0.68; = 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02-0.38; = 0.001). Among ovarian cancer patients, carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS. .
BRCA2 在同源重组中起着核心作用,通过将 RAD51 加载到 DNA 断裂处。本研究的目的是确定基因 RAD51 结合域(RAD51-BD;外显子 11)中的突变位置是否影响卵巢癌患者的临床结局。确定了 353 名接受基因胚系检测的卵巢癌患者的研究队列,这些患者接受了 基因和 基因的遗传种系检测。无进展生存期(PFS)、铂无间期(PFI)和总生存期(OS)进行了分析。使用卵巢癌的癌症基因组图谱(TCGA)队列(= 316)作为验证队列。在研究队列中,78 例患者为胚系突变的携带者。在调整了FIGO 分期和大体残留疾病后,RAD51-BD 截断突变的携带者 5 年 PFS 显著延长[58%;调整 HR,0.36;95%CI,0.20-0.64;= 0.001],PFI 也延长(29.7 与 15.5 个月,= 0.011),与非携带者相比。该基因其他区域突变的携带者 5 年 PFS 无延长(28%,调整 HR,0.67;95%CI,0.42-1.07;= 0.094)或 PFI 无延长(19 与 15.5 个月,= 0.146)。在 TCGA 队列中,只有 RAD51-BD(外显子 11)中携带胚系或体细胞突变的 携带者 5 年 PFS 延长(46%;调整 HR,0.30;95%CI,0.13-0.68;= 0.004)和 5 年 OS 延长(78%;调整 HR,0.09;95%CI,0.02-0.38;= 0.001)。在卵巢癌患者中,RAD51-BD(外显子 11)突变的携带者 PFS、PFI 和 OS 延长。