Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
JCO Glob Oncol. 2024 Jun;10:e2300454. doi: 10.1200/GO.23.00454.
Genetic variants of ovarian cancer (OV) show ethnic differences, but data from the Chinese population are still insufficient. Here, we elucidate the inheritance landscape in Chinese patients with OV and examine the functional implications of a Chinese-enriched variant.
Between 2015 and 2018, 373 consecutive patients with OV were prospectively enrolled. Variants of , other homologous recombination repair (HRR) genes, and DNA mismatch repair (MMR) genes were analyzed using next-generation sequencing. An enriched variant was identified, and its functional effects were examined using Cell Counting Kit-8, colony formation, transwell migration, and drug sensitivity assays.
Overall, 31.1% (116/373) of patients had at least one pathogenic or likely pathogenic germline variant. and accounted for 16.09% and 5.36%, respectively, with one patient having both variants. In addition, 32 (8.58%) patients carried other HRR gene variants, whereas three (0.8%) patients had MMR gene variants. The variant ranked third (8/373, 2.1%), and its rate was much higher than that in other populations. Remarkably, all eight patients harbored the K91fs variant (c.270_271dup, p.Lys91Ilefs*13) and demonstrated satisfactory platinum response and favorable prognosis. This variant confers enhanced sensitivity to poly (ADP-ribose) polymerase inhibitors in OV cells. However, the effects on platinum sensitivity were inconsistent across different cell lines. Against the background of the variant, K91fs variant showed increased sensitivity to cisplatin.
Our study revealed the inheritance landscape of OV and identified an enriched variant in Chinese patients with OV. This can serve as an important reference for OV management and a potential therapeutic target.
卵巢癌（OV）的遗传变异存在种族差异，但来自中国人群的数据仍然不足。在这里，我们阐明了中国OV 患者的遗传特征，并研究了一个富含中国人群的变异的功能意义。
2015 年至 2018 年，前瞻性纳入 373 例 OV 连续患者。使用下一代测序分析 、其他同源重组修复（HRR）基因和 DNA 错配修复（MMR）基因的变异。鉴定一个富含 的变异，并使用细胞计数试剂盒-8、集落形成、Transwell 迁移和药敏试验来检测其功能影响。
总体而言，31.1%（116/373）的患者至少有一个致病性或可能致病性的种系变异。和分别占 16.09%和 5.36%，其中一名患者同时携带这两种变异。此外，32 例（8.58%）患者携带其他 HRR 基因变异，3 例（0.8%）患者携带 MMR 基因变异。的变异排名第三（8/373，2.1%），其发生率明显高于其他人群。值得注意的是，所有 8 例患者均携带 K91fs 变异（c.270_271dup，p.Lys91Ilefs*13），并表现出满意的铂类反应和良好的预后。该变异赋予 OV 细胞对聚（ADP-核糖）聚合酶抑制剂的敏感性增加。然而，在不同的细胞系中，对铂类药物敏感性的影响不一致。在 的背景下，K91fs 变异增加了对顺铂的敏感性。
本研究揭示了 OV 的遗传特征，并鉴定了中国 OV 患者中富含 的变异。这可为 OV 的管理提供重要参考，并可能成为潜在的治疗靶点。
