Poly (ADP-ribose) polymerase inhibitors targeting BRCA1/2 mutations are available for treating patients with high-grade serous ovarian cancer. These treatments may be more appropriately directed to patients who might respond if the tumor tissue is additionally tested by next-generation sequencing with a multi-gene panel and Sanger sequencing of a blood sample. In this study, we compared the results obtained using the next-generation sequencing multi-gene panel to a known germline BRCA1/2 mutational state determined by conventional Sanger sequencing to evaluate the landscape of somatic mutations in high-grade serous ovarian cancer tumors. Cancer tissue from 98 patients with high-grade serous ovarian cancer who underwent Sanger sequencing for germline BRCA1/2 analysis were consecutively analyzed for somatic mutations using a next-generation sequencing 170-gene panel. Twenty-four patients (24.5%) showed overall BRCA1/2 mutations. Seven patients (7.1%) contained only somatic BRCA1/2 mutations with wild-type germline BRCA1/2, indicating acquired mutation of BRCA1/2. Three patients (3.1%) showed reversion of germline BRCA1 mutations. Among the 14 patients (14.3%) with both germline and somatic mutations in BRCA1/2, two patients showed different variations of BRCA1/2 mutations. The next-generation sequencing panel test for somatic mutation detected other pathogenic variations including RAD51D and ARID1A, which are possible targets of poly (ADP-ribose) polymerase inhibitors. Compared to conventional Sanger sequencing alone, next-generation sequencing-based tissue analysis increased the number of candidates for poly (ADP-ribose) polymerase inhibitor treatment from 17.3% (17/98) to 26.5% (26/98). Somatic mutation analysis by next-generation sequencing, in addition to germline BRCA1/2 mutation analysis, should become the standard of care for managing women with high-grade serous ovarian cancer to widen the indication of poly (ADP-ribose) polymerase inhibitors.

中文翻译：

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高度浆液性卵巢癌患者生殖系和体细胞BRCA1 / 2的突变情况

靶向BRCA1 / 2突变的聚（ADP-核糖）聚合酶抑制剂可用于治疗患有高度浆液性卵巢癌的患者。如果通过多基因组的下一代测序和血样的Sanger测序额外测试肿瘤组织，则这些治疗可能更适合于可能有反应的患者。在这项研究中，我们将使用下一代多基因测序技术与常规Sanger测序确定的已知种系BRCA1 / 2突变状态进行比较，以评估高级浆液性卵巢癌肿瘤中体细胞突变的情况。对来自98位进行了Sanger测序以进行种系BRCA1 / 2分析的高级浆液性卵巢癌患者的癌症组织，使用新一代170序列测序技术连续分析了体细胞突变。24名患者（24.5％）显示出整体BRCA1 / 2突变。7名患者（7.1％）仅包含带有野生型种系BRCA1 / 2的体细胞BRCA1 / 2突变，表明获得性BRCA1 / 2突变。三名患者（3.1％）显示出生殖细胞BRCA1突变回复。在BRCA1 / 2的种系突变和体细胞突变的14例患者中（14.3％），两名患者的BRCA1 / 2突变表现出不同的变异。用于体细胞突变的下一代测序小组测试检测到其他病原性变异，包括RAD51D和ARID1A，它们可能是聚（ADP-核糖）聚合酶抑制剂的靶标。与仅传统的Sanger测序相比，基于下一代测序的组织分析将聚（ADP-核糖）聚合酶抑制剂治疗候选物的数量从17.3％（17/98）增至26.5％（26/98）。除种系BRCA1 / 2突变分析外，通过下一代测序进行的体细胞突变分析应成为治疗患有高级别浆液性卵巢癌的妇女以扩大聚（ADP-核糖）聚合酶抑制剂适应症的护理标准。