Table_1_Next-Generation Sequencing Reveals a Very Low Prevalence of Deleterious Mutations of Homologous Recombination Repair Genes and Homologous Recombination Deficiency in Ovarian Clear Cell Carcinoma.xlsx

Ovarian clear cell carcinoma (OCCC) is aggressive and drug-resistant. The prevalence of homologous recombination repair (HRR) gene mutations and homologous recombination deficiency (HRD) remains largely unknown. It is also not clear whether the commonly used molecular-based classification for endometrial carcinoma (EC) is potentially applicable in OCCC. In this study, surgically resected samples were collected from 44 patients with OCCC. Genomic alterations were determined using next-generation sequencing. HRD was estimated by genomic instability. Of 44 patients with OCCC, two (4.5%) harbored likely pathogenic mutations in HRR genes. Notably, no pathogenic or likely pathogenic mutations were found in BRCA1/2. A total of 24 variants of uncertain significance (VUS) in HRR-related genes occurred in 18 (40.9%) patients. HRD was observed in only one case (2.3%). In addition, TP53 mutation and microsatellite instability-high (MSI-H) were identified in three patients (6.8%) and in one patient (2.3%), respectively. TP53 mutation was significantly associated with disease-free survival and overall survival. No POLE mutations were found. In conclusion, our results revealed a very low prevalence of HRR gene mutations and HRD in OCCC. Moreover, TP53 mutations and MSI-H are uncommon, while POLE mutations are extremely rare in OCCC. Our findings indicate that the evaluation of HRR gene mutations, HRD status, POLE mutations, and MSI-H may have limited clinical significance for OCCC treatment and prognostic stratification.

卵巢透明细胞癌（Ovarian clear cell carcinoma, OCCC）是一类侵袭性强且具有药物耐受性的恶性肿瘤。目前，同源重组修复（homologous recombination repair, HRR）基因突变与同源重组缺陷（homologous recombination deficiency, HRD）在OCCC中的患病率仍未明确，且子宫内膜癌（endometrial carcinoma, EC）通用的分子分型方案是否可推广应用于OCCC亦尚未可知。本研究纳入44例经手术切除的OCCC患者样本，采用下一代测序技术检测基因组变异，并通过基因组不稳定性评估HRD状态。在44例OCCC患者中，仅2例（4.5%）携带HRR基因的可能致病性突变；值得注意的是，未在BRCA1/2基因中检出致病性或可能致病性突变。另有18例（40.9%）患者的HRR相关基因中存在24个意义未明变异（variants of uncertain significance, VUS）。仅1例（2.3%）患者被检出HRD。此外，3例（6.8%）患者检出TP53突变，1例（2.3%）患者检出高度微卫星不稳定（microsatellite instability-high, MSI-H）。TP53突变与患者的无病生存期及总生存期显著相关。本研究未检出POLE基因突变。综上，本研究结果显示OCCC中HRR基因突变与HRD的患病率极低。此外，TP53突变与MSI-H在OCCC中较为少见，而POLE基因突变则极为罕见。本研究结果提示，HRR基因突变检测、HRD状态评估、POLE基因突变检测及MSI-H检测在OCCC的临床治疗与预后分层中应用价值有限。