Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, Minnesota.
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
Sci Rep. 2014 Feb 7;4:4026. doi: 10.1038/srep04026.
We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.
我们在一个大型的、有详细注释的患者群体中，考虑到 BRCA1、BRCA2 和 RAD51C，评估了上皮性卵巢癌（EOC）中的同源重组缺陷（HRD）表型。我们使用 NGS 和全基因组甲基化阵列评估了这些基因的胚系有害突变（n=899）、体细胞突变（n=279）和表观遗传改变（n=482）。在 32 名（3.6%）BRCA1、28 名（3.1%）BRCA2 和 26 名（2.9%）RAD51C 的患者中发现了有害的胚系突变。在 10 名体细胞测序的患者中发现了有害的改变，6 名（2.1%）在 BRCA1 中，4 名（1.4%）在 BRCA2 中。52 名（10.8%）患者的 BRCA1 或 RAD51C 甲基化。任何基因中存在胚系或体细胞改变的 HRD 患者更有可能患有高级别浆液性卵巢癌，诊断年龄更早，并有卵巢癌和/或乳腺癌家族史。HRD 表型在高级别浆液性 EOC 中最为常见。识别具有 HRD 表型的 EOC 患者可能有助于定制特定的治疗方法。
