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

被引:14
作者
Liu, Hangqi [1 ]
Zhang, Zhiwen [1 ]
Chen, Longyun [1 ]
Pang, Junyi [1 ]
Wu, Huanwen [1 ]
Liang, Zhiyong [1 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Mol Pathol Res Ctr, Dept Pathol,State Key Lab Complex Severe & Rare D, Beijing, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2022年 / 11卷
基金
中国国家自然科学基金;
关键词
ovarian clear cell carcinoma; homologous recombination repair gene; homologous recombination deficiency; molecular classification; next-generation sequencing; EXPRESSION; VARIANTS;
D O I
10.3389/fonc.2021.798173
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:9
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