Abstract 4355: Characterizing HRD in ovarian cancer: Insights from copy number signatures

Abstract Copy number changes are defining features in ovarian cancers. Two distinct methods by Steele et al. and Drews et al., published back-to-back in 2022, detail features and categories of copy number signatures. However, these methods have not been benchmarked for ovarian cancer. Mutational signatures are pivotal in understanding cancer biology and serve as predictive and prognostic biomarkers. This study aims to examine the landscape of copy number signatures to characterize the diversity of Homologous Recombination (HR) impairment within ovarian cancer. While assessing Homologous Recombination Deficiency (HRD) is crucial for targeted treatments, current HRD tests lack clarity. Using signature extraction tools SigProfilerExtractor and CINSignature, we analyzed whole-genome sequencing data (mean depth 100x) from 416 ovarian cases from Genomics England (GeL), employing both copy number signature methods. Among the signatures extracted, HRD signature CN17 from Steele et al. methodology was identified in 37% of the samples and primarily found in the high-grade serous ovarian cancer (HGSOC) subtype (77%). Additionally, higher exposure levels (median of 0.4 in n=154 compared to median of 0.29 in n=416) of Drews et al. methodology’s most complex HRD signature, CX3, was detected in samples exhibiting CN17 activity. This ongoing exploration of the copy number signatures landscape works towards identifying the spectrum of HR impairment, aiming to benchmark these two methods for a standardized diagnostic tool. This study contributes to our understanding of the mutational landscape of ovarian cancer and its potential implications for prevention and personalized treatment strategies. Citation Format: Aliah Hawari, Avraam Tapinos, Claire J. Kramer, Andreas J. Gruber, Richard Houlston, James Brenton, David Wedge. Characterizing HRD in ovarian cancer: Insights from copy number signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4355.