携带胚系同源重组修复基因突变的卵巢上皮性癌临床特点

Clinical Characteristics of Patients with Epithelial Ovarian Cancer Carrying Homologous Recombination Repair Genes Germline Mutation

目的:探索携带胚系同源重组修复(HRR)基因突变的卵巢上皮性癌的临床特征、预后及家系特征。方法:选择2018年1月至2020年2月就诊于北京大学第三医院卵巢上皮性癌患者121例,采用二代测序技术对所有患者外周血HRR基因进行全外显子检测。分别对携带有害胚系HRR基因(致病性和可能致病性)突变的患者(有害突变组)和未携带HRR基因(包含良性、可能良性)突变的患者(未携带突变组)分析其临床特点、预后及个人/亲属肿瘤家族史。结果:121例卵巢上皮性癌患者HRR基因总突变率为29.8%(36/121),其中BRCA1占63%,RAD51D占13%,BRCA2占10%。有害突变组和未携带突变组的患者病理类型构成差异有统计学意义(P=0.018),有害突变组患者均为高级别浆液性癌(100%),未携带突变组高级别浆液性癌比例为72.2%(52/72)。有害突变组有5例(5/36)患者同时罹患其他原发恶性肿瘤,与未携带突变组(2/72)相比,差异有统计学意义(P=0.030)。有害突变组患者一级亲属罹患肿瘤阳性率69.4%(25/36)与未携带突变组31.9%(23/72)相比,差异有统计学意义(P<0.001)。有害突变组均为铂类敏感(100%),与未携带突变组(90.3%)铂类敏感相比差异无统计学意义(P=0.093)。有害突变组与未携带突变组发病年龄、分期、首发症状、无进展生存期比较差异均无统计学意义(P>0.05)。结论:卵巢上皮性癌患者特别是高级别浆液性癌患者应进行遗传咨询,重视个人及一级亲属肿瘤史采集。携带有害胚系HRR基因突变患者同时罹患其他恶性肿瘤风险高。对HRR基因的检测,有利于对患者进行精准治疗同时也有助于发现其亲属中的高危人群并早期干预、预防肿瘤发生。

Objective:To observe the clinical characteristics, prognosis and family history of cancer of patients with epithelial ovarian cancer carrying homologous recombination repair(HRR)genes germline mutation.Methods:121 patients with epithelial ovarian cancer were enrolled in our study from January 2018 to February 2020 in Peking University Third Hospital.Whole-exome of HRR genes were analyzed in peripheral blood of all patients using next generation sequencing.Parametric and nonparametric test methods were used to compare the clinical characteristicsand family history of cancer.Log rank test and Kaplan-Meier survival analyses were performed to analyze the prognosis of patients.Results:The mutation rate of HRR genes was 29.8%(36/121),in which BRCA1 accounted for 63%,RAD51 D accounted for 13%,and BRCA2 accounted for 10%.There was a statistically significant difference in the pathological type composition of patients in the group with deleterious mutations and the group without carrying mutations(100% vs 72.2%,P=0.018).There were 5 patients with other primary malignant tumors in the 36 patients inmutation group, and the difference was statistically significant compared with the non-carrier group(2/72)(P=0.030).The positive rate of malignancy in first-degree relatives of patients with deleterious mutation was 69.4%(25/36) and 31.9%(23/72) of patients without deleterious mutation(P<0.001).The proportion of platinum-sensitive patients in the group with deleterious mutations(100%) differed from the group not carrying mutations(90.3%)(P=0.093).There was no significant difference in age, stage, first symptoms and progression free survival between the two groups(P>0.05).Conclusions:Patients with epithelial ovarian cancer, especially those with high-grade serous cancer, should undergogenetic counseling, with emphasis on personal and first-degree relative tumor history collection.Patients with deleterious HRR genes germline mutationare more likely to simultaneously suffer from other malignant tumors than the rest.Testing for HRR gene is helpful for precise treatment of patients and also for early intervention and prevention of tumors among their relatives who are at high risk.