Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China.
BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China.
J Ovarian Res. 2019 Aug 31;12(1):80. doi: 10.1186/s13048-019-0560-y.
Multiple targeted gene sequencing is seldom performed in both germline and somatic testing for ovarian cancer. This study is to evaluate the specific genetic alterations, including both somatic and germline mutations, in Chinese patients with epithelial ovarian cancer (EOC) in a prospective cohort study.
Mutations in a customed 21-gene panel that included BRCA1, BRCA2, and 19 other tumor suppressor genes related to homologous recombination (HR) deficiency or non-HR deficiency were detected by targeted exon capture and next-generation sequencing (NGS) technology across all coding exons and exon-intron (±20 base pairs) boundaries. Patients were enrolled consecutively and unselectively without age or family history consideration. Sixty-two unselected patients with epithelial ovarian cancer were enrolled in our study to be tested for paired somatic and germline mutations. All patients were tested using a 21-gene panel that included BRCA1, BRCA2, CHEK2, PALB2, BRIP1, TP53, PTEN, STK11, CDH1, ATM, BARD1, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PMS1, PMS2, RAD50, and RAD51C.
Mutation analysis revealed that 77.4% (48/62) of patients carried one or more of 64 identified genetic alterations, including 19 germline and 45 somatic deleterious mutations. Twelve individuals shared both germline and somatic mutations. BRCA mutants existed in 17 of 62 (27.4%) patients. Of the 64 mutations detected, 46 (74.2%) were in 7 other HR or non-HR genes, including TP53, PTEN, ATM, CHEK2, PALB2, RAD51C, and STK11. In somatic mutation analysis, TP53 showed frequent pathogenic or likely pathogenic mutations in 56.5% (35/62) of enrolled cases, among which six cases harbored a loss of heterozygosity.
This is the first report of multi-gene panel testing for germline and somatic mutations among Chinese EOC patients, which revealed a broader deleterious variants than only BRCA testing.
Registration No. NCT03015376, clinicaltrials.gov , registered on January 10, 2017.
在卵巢癌的种系和体细胞检测中，很少同时进行多个靶向基因测序。本研究旨在通过靶向外显子捕获和下一代测序（NGS）技术，对中国上皮性卵巢癌（EOC）患者进行前瞻性队列研究，评估特定的遗传改变，包括体细胞和种系突变。
通过靶向外显子捕获和下一代测序（NGS）技术，在所有编码外显子和外显子-内含子（±20 个碱基对）边界检测定制的 21 基因面板中的突变，该面板包括 BRCA1、BRCA2 和 19 个其他与同源重组（HR）缺陷或非 HR 缺陷相关的肿瘤抑制基因。连续、非选择性地招募患者，不考虑年龄或家族史。本研究共招募了 62 名未选择的上皮性卵巢癌患者进行配对的体细胞和种系突变检测。所有患者均使用包括 BRCA1、BRCA2、CHEK2、PALB2、BRIP1、TP53、PTEN、STK11、CDH1、ATM、BARD1、MLH1、MRE11A、MSH2、MSH6、MUTYH、NBN、PMS1、PMS2、RAD50 和 RAD51C 在内的 21 个基因panel 进行检测。
突变分析显示，77.4%（48/62）的患者携带一种或多种 64 种已识别的遗传改变，包括 19 种种系和 45 种体细胞有害突变。12 名患者同时存在种系和体细胞突变。17 名患者（27.4%）为 BRCA 突变。在 64 种检测到的突变中，46 种（74.2%）位于其他 7 个 HR 或非 HR 基因中，包括 TP53、PTEN、ATM、CHEK2、PALB2、RAD51C 和 STK11。在体细胞突变分析中，TP53 在 56.5%（35/62）的入组病例中显示出频繁的致病性或可能致病性突变，其中 6 例存在杂合性丢失。
这是中国上皮性卵巢癌患者进行种系和体细胞突变多基因panel 检测的首次报告，揭示了比仅 BRCA 检测更广泛的有害变异。
NCT03015376，clinicaltrials.gov，于 2017 年 1 月 10 日注册。
