Genomic Analyses of Germline and Somatic Variation in High-Grade Serous Ovarian Cancer

The goal of this study was to identify and characterize germline and somatic genetic variation in women with high grade serous ovarian cancers treated at a single cancer center and their associations with relapse-free and overall survival. We conducted paired tumor/normal targeted next-generation sequencing of 577 genes in pathways of DNA repair, response to DNA damage, cell-cycle regulation, programmed cell death, MAPK, and P13K/AKT/MTOR signaling in 114 tumors from 71 women. In addition, we investigated single copy number alterations (SCNAs) and loss of heterozygosity in a subset of 61 tumors. We validated our results with data from ovarian tumors in TCGA. Our results were similar to other studies of high-grade serous carcinomas. As an example, we found that approximately one third of... (for more see dbGaP study page.)

本研究旨在鉴定并表征在单一癌症中心接受治疗的高级别浆液性卵巢癌女性患者的生殖系与体细胞遗传变异，以及这些变异与无复发生存期和总生存期的关联。我们对71名女性的114份肿瘤样本开展了配对肿瘤-正常组织靶向二代测序，测序覆盖了DNA修复、DNA损伤应答、细胞周期调控、程序性细胞死亡、MAPK以及PI3K/AKT/mTOR信号通路共577个基因。此外，我们还对61份肿瘤样本组成的亚群开展了单拷贝数改变（single copy number alterations, SCNAs）与杂合性缺失（loss of heterozygosity）的分析。本研究通过癌症基因组图谱（The Cancer Genome Atlas, TCGA）中的卵巢肿瘤数据对研究结果进行了验证，所得结果与其他高级别浆液性癌相关研究的结论一致。例如我们发现约三分之一的……（更多详情请参见dbGaP研究页面）。