BRCA1基因c.5470_5477del突变卵巢癌临床病理特征及预后分析  

Clinical characteristics and survival analysis of Chinese ovarian cancer with BRCA1 c.5470_5477del germline mutation

作　　者：袁华 姚洪文 董林 李晓光 李楠 马绍康 吴令英 李宁 YUAN Hua;YAO Hongwen;DONG Lin;LI Xiaoguang;LI Nan;MA Shaokang;WU Lingying;LI Ning(Department of Gynecologic Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021,China;Department of Pathology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021,China)

机构地区：[1]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院,妇科,北京100021 [2]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院,病理科,北京100021

出　　处：《中国妇产科临床杂志》2023年第4期345-349,共5页Chinese Journal of Clinical Obstetrics and Gynecology

基　　金：国家自然科学基金(82172652);中国癌症基金会北京希望马拉松专项基金(LC2020A10)。

摘　　要：目的探讨携带乳腺癌易感基因1(BRCA1)c.5470_5477del突变卵巢癌的临床病理特征及预后情况。方法采用二代测序技术,对760例于2001年1月至2020年9月在本院接受治疗、组织病理学确诊的上皮性卵巢癌患者的肿瘤组织进行BRCA1/2基因突变检测,对携带致病突变者通过唾液或血液检测确定是否为胚系突变。对BRCA1基因c.5470_5477del突变卵巢癌诊断年龄、家族史、个人肿瘤史、病理分期、病理类型、化疗敏感性、聚腺苷二磷酸核糖聚合酶(PARP)抑制剂疗效、预后等指标进行分析。结果760例上皮性卵巢癌患者中,214例患者携带BRCA1/2基因致病性胚系或体系突变,突变频率为28.2%(214/760)。其中BRCA1基因c.5470_5477del突变频率最高(2.8%,21/760),且均为胚系突变,来自不同家系。该突变占BRCA1基因所有突变的13.5%(21/156)。BRCA1 c.5470_5477del突变卵巢癌患者的中位发病年龄为52岁(36~67岁)。81.0%(17/21)的患者诊断年龄≥50岁,仅1例患者在40岁前发病。9例(42.9%,9/21)患者具有乳腺癌或卵巢癌家族史;4例(19.0%,4/21)患者有乳腺癌病史。8例(38.1%,8/21)患者无恶性肿瘤家族史和个人乳腺癌等恶性肿瘤病史。90.5%(19/21)的患者手术病理分期为FIGOⅢ~Ⅳ期。共有7例(33.3%,7/21)患者接受PARP抑制剂一线维持治疗。中位随访34.5个月(12.3~111.0个月),中位无进展生存时间(PFS)为25.4个月,2年PFS为57.4%。接受一线PARP抑制剂维持治疗的患者中,2年PFS为80.0%。结论BRCA1基因c.5470_5477del突变是中国卵巢癌患者最常见的BRCA1/2基因胚系突变。无恶性肿瘤家族史或个人史者也应警惕携带该胚系致病突变。不同于其他BRCA1突变,该突变携带者的预防性手术时间也许可考虑适当推迟。携带该突变的卵巢癌患者总体预后较好,有必要接受PARP抑制剂一线维持治疗。Objective The objective of this study was to investigate the clinical characteristics and prognosis of Chinese ovarian cancer patients with the BRCA1 c.5470_5477del germline mutation.Methods We conducted next-generation sequencing(NGS)for the entire coding regions and exon/intron boundaries of the BRCA1 and BRCA2 genes in 760 Chinese ovarian cancer patients treated at our institution from 2001 to 2020.Clinicopathological characteristics,treatment modalities,and outcomes were assessed for ovarian cancer patients with BRCA1 c.5470_5477del germline mutation.Results BRCA1/2 germline or somatic pathogenic mutations were detected in 28.2%(214/760)of patients in this cohort.BRCA1 c.5470_5477del germline mutation was detected in 2.8%(21/760)of patients,which was the most frequency BRCA1/2 pathogenic variant of these patients.21 patients came from 21 unrelated families carried this pathogenic variant.This pathogenic mutation represented for 13.5%(21/156)of BRCA1 pathogenic mutations.In the current study,patients median age at diagnosis was 52 years(range:36-67 years).81.0%(17/21)of them were diagnosed after 50 years.Only one patient diagnosed before the age of 40.Nine patients(42.9%)had a family history of ovarian or breast cancer while four patients(19.0%)had a personal history of breast cancer.And 8 patients(38.1%)had no family history of ovarian or breast cancer,and no personal history of breast cancer.The majority of patients(90.5%)were diagnosed at stageⅢ/Ⅳ.Seven patients(33.3%)received PARP inhibitor first line maintenance therapy after adjuvant chemotherapy.The median follow-up was 34.5 months(range:12.3-111.0 months).Median progression-free survival(PFS)for the entire cohort was 25.4 months.2-year PFS was 57.4%.2-year PFS for patients receiving PARPi maintenance was 80.0%.Conclusions The BRCA1 c.5470_5477del germline mutation is the most common BRCA1/2 pathogenic mutation in Chinese ovarian cancer patients.Even in the absence of a family or personal history of ovarian or breast cancer,individuals should be cau

关 键 词：BRCA1基因 c.5470_5477del突变 卵巢癌 临床特征 预后 

分 类 号：R737.31[医药卫生—肿瘤]