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
Hangqi Liu, Zhiwen Zhang, Longyun Chen, Junyi Pang, Huanwen Wu, Zhiyong Liang
Abstract
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.