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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

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 endome...

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Detalles Bibliográficos
Autores principales: Liu, Hangqi, Zhang, Zhiwen, Chen, Longyun, Pang, Junyi, Wu, Huanwen, Liang, Zhiyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791260/
https://www.ncbi.nlm.nih.gov/pubmed/35096598
http://dx.doi.org/10.3389/fonc.2021.798173
Descripción
Sumario: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.