Differential Sensitivity of Germline and Somatic Variants to PARP Inhibitor in High-Grade Serous Ovarian Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Sep 28

PMID 37762485

Authors

Julie A Vendrell

Iulian O Ban

Isabelle Solassol

Patricia Audran

Simon Cabello-Aguilar

Delphine Topart

Clothilde Lindet-Bourgeois

Pierre-Emmanuel Colombo

Eric Legouffe

Veronique DHondt

Michel Fabbro

Jerome Solassol

Affiliations

Soon will be listed here.

Abstract

Purpose: The introduction of PARP inhibitors (PARPis) as a treatment option for patients with high-grade serous ovarian cancer (HGSOC) modified the approach of testing worldwide. In this study, we aim to evaluate the impact of and variants on treatment response and survival outcomes in patients diagnosed in our institution.

Methods: A total of 805 HGSOC samples underwent and variant detection by using next-generation sequencing (NGS). Among them, a pathogenic alteration was detected in 104 specimens. Clinicopathological features and germline status were recovered, and alteration types were further characterized. The clinical significance of variant type in terms of response to chemotherapy and to PARPis as well as overall survival were evaluated using univariate analysis.

Results: In our cohort, 13.2% of the HGSOC samples harbored a pathogenic or variant, among which 58.7% were inherited. No difference was observed between germline and somatic variants in terms of the gene altered. Interestingly, patients with somatic variants only (no germline) demonstrated better outcomes under PARPi treatment compared to those with germline ones.

Conclusion: The determination of the inheritance or acquisition of and alterations could provide valuable information for improving management strategies and predicting the outcome of patients with HGSOC.

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