Improved detection of homologous recombination deficiency in Chinese patients with ovarian cancer: a novel non‐exonic single‐nucleotide polymorphism‐based next‐generation sequencing panel

Abstract

As homologous recombination deficiency (HRD) is a biomarker to predict the efficiency of PARP inhibitor treatment, this study developed a non‐exonic single‐nucleotide polymorphism (SNP)‐based targeted next‐generation sequencing panel and comprehensively examined it both on standard and clinical ovarian cancer tissues. The HRD scores calculated by the panel and whole‐genome sequencing were consistent, with the analysis by sequenza being the most reliable. The results on clinical samples revealed that the panel performed better in HRD analysis compared with the SNP microarray. There are several distinctions between this newly developed kit and reported HRD detection panels. First, the panel covers only 52 592 SNPs, which makes it capable of detecting genomic instability. Secondly, all the SNPs are non‐exonic; as a result, the panel can be used cooperatively with any exon panel. Thirdly, all the SNPs selected have a high minor allele frequency in Chinese people, making it a better choice for HRD detection in Chinese patients. In summary, this panel shows promise as a clinical application to guide PARP inhibitors or platinum drugs used in the treatment of ovarian and other cancers.

Keywords

• Chinese population
• CNV
• HRD
• ovarian cancer
• SNP‐based NGS panel