Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China.
Zhejiang Cancer Hospital, Hangzhou, China.
Cancer Med. 2019 Jul;8(8):3928-3935. doi: 10.1002/cam4.2243. Epub 2019 May 24.
High-grade serous ovarian carcinoma (HGSOC) is a major form of ovarian epithelial tumor that is often diagnosed only at an advanced stage when it is already highly aggressive. We performed comprehensive genomic profiling using an analytically validated clinical next-generation sequencing assay to identify genomic alterations in 450 cancer-related genes in a cohort of 88 Chinese HGSOC patients. Overall, we detected 547 genomic alterations with an average of 6.2 alterations per tumor. Most of these HGSOC tumors had low tumor mutation burden and were microsatellite stable. Consistent with earlier studies, TP53 mutations were present in the majority (96.6%) of the tumors studied, and mutations in BRCA1/2 that affect DNA repair were also detected frequently in 20.5% of the tumors. However, we observed a 10.2% of mutated genes in the Ras/Raf pathway, all co-occurring with TP53 mutations in the same tumor, which was unrecognized previously. Our results show that in HGSOC patients, there may be an unrecognized co-occurrence of TP53 mutations with mutations in Ras/Raf pathway.
高级别浆液性卵巢癌（HGSOC）是一种主要的卵巢上皮性肿瘤，通常在晚期才被诊断出来，此时肿瘤已经高度侵袭性。我们使用经过分析验证的临床下一代测序检测对 88 名中国 HGSOC 患者的队列中的 450 个癌症相关基因进行了全面的基因组分析，以鉴定基因组改变。总体而言，我们检测到 547 个基因组改变，每个肿瘤的平均改变为 6.2 个。这些 HGSOC 肿瘤中的大多数具有低肿瘤突变负担和微卫星稳定性。与早期研究一致，研究中大多数肿瘤（96.6%）存在 TP53 突变，并且在 20.5%的肿瘤中也经常检测到影响 DNA 修复的 BRCA1/2 突变。然而，我们观察到 Ras/Raf 通路中有 10.2%的突变基因，所有这些基因都与同一肿瘤中的 TP53 突变同时发生，这是以前未被认识到的。我们的结果表明，在 HGSOC 患者中，TP53 突变与 Ras/Raf 通路中的突变可能存在未被认识到的共同发生。
