体细胞
种系突变
生殖系
外显子组测序
癌症研究
浆液性液体
肿瘤科
外显子组
生物
同源重组
奥拉帕尼
内科学
突变
医学
基因
遗传学
聚ADP核糖聚合酶
聚合酶
作者
Viktor Hlavac,Petr Holy,Radka Václavíková,Lukáš Rob,Martin Hruda,Marcela Mrhalová,Petr Černaj,Jiří Bouda,Pavel Soucek
标识
DOI:10.26508/lsa.202201551
摘要
Epithelial ovarian carcinoma (EOC) is highly fatal because of the risk of resistance to therapy and recurrence. We performed whole-exome sequencing of blood and tumor tissue pairs of 50 patients with surgically resected EOC. Compared with sensitive patients, platinum-resistant patients had a significantly higher somatic mutational rate in TP53 and lower in several genes from the Hippo pathway. We confirmed the pivotal role of somatic mutations in homologous recombination repair genes in platinum sensitivity and favorable prognosis of EOC patients. Implementing the germline homologous recombination repair profile significantly improved the prediction. In addition, distinct mutational signatures, for example, SBS6, and overall mutational load, somatic mutations in PABPC1 , PABPC3 , and TFAM co-segregated with the resistance status, high-grade serous carcinoma subtype, or overall survival of patients. We generated germline and somatic genetic landscapes of prognostically different subgroups of EOC patients for further follow-up studies focused on utilizing the observed associations in precision oncology.
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