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基因突变位置与卵巢癌患者的生存情况。

Location of Mutation in Gene and Survival in Patients with Ovarian Cancer.

机构信息

Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.

Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France.

出版信息

Clin Cancer Res. 2018 Jan 15;24(2):326-333. doi: 10.1158/1078-0432.CCR-17-2136. Epub 2017 Oct 30.

Abstract

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. .

摘要

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。

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