Abstract 2064: Homologous recombination repair somatic/germline mutation detection in plasma by next-generation sequencing in Chinese solid tumor patients

Abstract

Abstract Purpose: PARP inhibitors (PARPis) have been approved for germline and/or somatic BRCA-mutated ovarian cancer, breast cancer, pancreatic cancer and homologous recombination repair gene (HRR)-mutated prostate cancer. Emerging evidence has shown that antitumor activity of PARPis could expand to other HRR-mutated solid tumors. Therefore, efficient and timely methods to detect both somatic and germline HRR mutations using tissue or blood are urgently needed. Here, we first specially reported the prevalence of HRR mutation in plasma samples using Next-generation sequencing (NGS). Methods: A total of 1601 paired plasma-white blood cell samples and 3404 paired tumor-white blood from Chinese solid tumor patients were collected between October 2019 and October 2020. The samples were assessed with targeted NGS of circulating tumor DNA (ctDNA) or tumor tissue DNA (ttDNA) to detect deleterious somatic and germline mutations in 16 core HR genes in a CLIA-certified laboratory. Results: Overall, 165/1601 (10.3%) patients had at least one somatic or germline HRR gene mutations by ctDNA-based NGS analysis. The most commonly mutated tumor types were endometrium (42.9%, n=7), ovary (38.5%, n=13), prostate (27.8%, n=108), neuroendocrine (20%, n=5), breast (19%, n=42), melanoma (16.7%, n=6), stomach (15.8%, n=101), biliary tract (15.6%, n=64), cervix (12.5%, n=8), pancreas (11.4%, n=70), colorectum (9.8%, n=174) and bladder urinary tract (9.5%, n=21). Except for the four tumor types (endometrium, neuroendocrine, melanoma and cervix) with less than ten samples, the prevalence of HRR mutation was comparable with the ttDNA-based NGS data. Among HRR mutations, BRCA2 was the most commonly mutated gene (3.2%), followed by ATM (2.4%), BRCA1 (1.4%), CHEK2 (1.2%), BARD1 (0.7%), PALB2 (0.7%), CDK12 (0.7%) and FANCA (0.5%). Most of these data was similar to the results of ttDNA-based NGS. Moreover, slightly higher prevalence was found in BRCA2 (3.2% vs 2.5%) and CHEK2 (1.2% vs 0.7%), and slightly lower prevalence was found in ATM (2.4% vs 3.2%) and CDK12 (0.7% vs 1.4%). Conclusion: We first described the prevalence of somatic and/or germline HRR mutations detected by ctDNA-based NGS in a Chinese solid tumor cohort. Further prospective study is needed to compare the impact of the HRR status identified by ctDNA and ttDNA NGS on PARPis efficacy. Citation Format: Wei Zhu, Hui Chen, Bei Zhang, Xiaochen Zhao, Yuezong Bai. Homologous recombination repair somatic/germline mutation detection in plasma by next-generation sequencing in Chinese solid tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2064.