AcornHRD: A novel tool to identify homologous recombination deficiency events in whole genome sequencing data.

Abstract

e15078 Background: Recently, homologous recombination deficiency (HRD) scores are associated with the efficacy of Poly‐(ADP‐Ribose)‐Polymerase (PARP) inhibition and platinum-based chemotherapy in a variety of cancers. Evaluating HRD level in patients with cancers is becoming far more important and influential, so far, there is no standard method to be used in clinical. In this study, we developed an algorithm to detect HRD from next-generation sequencing (NGS) for finding additional patients may potentially benefit from target therapy. Methods: Forty-eight patients were enrolled, including breast cancer, ovarian cancer, prostatic cancer. Fifteen cell lines with breast cancer and endometrial carcinoma were collected from Cobioer biosciences co., LTD. Forty-eight Formalin-fixed, paraffin embedded (FFPE) samples and 15 cell lines were performed by DNA extracting. We developed an HRD score algorithm, termed as AcornHRD algorithm. HRD score was analyzed by whole-genome sequencing, and GATK mutect2 software was used to detect BRCA1/2mutation by deep sequencing. Results: BRCA1/2 deleterious mutations were observed in 20 patients (41.7%). HRD was explained by deficiencies in 17 patients (85.0%) with BRCA mutation, whereas eight HRD-high tumors were non- BRCA related (28.6%). Among BRCA wild-type patients, the corresponding percentage of HRD positive patients in breast cancer, ovarian cancer and prostate cancer were 36.3%, 37.5% and 11.1%, respectively. Similar results were also verified in the cell line datasets. The findings showed that 100% (3/3) BRCA1/2 deficient cell lines are also HRD-high. Furthermore, HRD scores were highly correlated with standard results in the cell line datasets. Conclusions: We here report the NGS-based HRD scores to distinguish similarly well between BRCA mutant and BRCA wild-type cases in a cohort of Chinese population. AcornHRD scores were highly associated with BRCA1/2 deficiency. AcornHRD algorithm can be a useful tool to detect HRD events in clinical settings.