Abstract 5755: Mutation profiling of homologous recombination-related (HRR) genes in sarcoma patients

Abstract

Abstract BACKGROUND: Homologous recombination deficiency (HRD) is associated with tumorigenesis. Therapy directed toward HRD has been approved in breast and ovarian cancer, however, whether there is a chance of benefit for patients with other cancers remains unknown. Herein, we investigated the mutation characteristics of homologous recombination-related (HRR) genes in Chinese patients with sarcoma to explore possible benefit opportunities for sarcoma patients. METHODS: The genetic landscape of HRR genes was assessed in 700 Chinese sarcoma patients with different subtypes including Rhabdomyosarcoma (RMS, n = 67), Liposarcoma (LPS, n = 58), Osteosarcoma (n = 34), Synovial sarcoma (n = 30), Leiomyosarcoma (n = 29), Ewing's sarcoma (EWS, n = 27), Angiosarcoma (n = 20), other rare (n = 375) and unknown subtypes (n = 60). Molecular profiles were performed by using next generation sequencing (NGS)-based Onco Panscan plus࣪ at Genetronhealth, a laboratory accredited by College of American Pathologists and Clinical Laboratory Improvement Amendments. RESULTS: Among the 700 patients, the overall mutation frequency of HRR genes was 19.0%. Correspond to specific subtypes, the mutation frequency of HRR genes were higher in Leiomyosarcoma (27.6%, 8/29), Angiosarcoma (25.0%, 5/20) and LPS (17.2%, 10/58) compared with RMS (14.9%, 10/67), Osteosarcoma (14.7%, 5/34), Synovial sarcoma (13.3%, 4/30) and EWS (3.7%, 1/27). ATRX was the most commonly mutated gene (5.1%, n = 36) and was preferentially identified in Leiomyosarcoma (10.3%) and Angiosarcoma. (10.0%), followed by ARID1A (3.1%, n = 22), ATM (2.1%, n = 15) and FANCA/C/D2/E/F/G/L (1.7%, n = 12). The median tumor mutational burden (TMB) was 2.35 in patients with HRD and 0.94 in patients without HRD. Although BRCA1 and BRCA2 mutations were less common overall (1.1% and 0.7%), a significant proportion of BRCA1 and BRCA2 mutations was found in Angiosarcoma, Liposarcoma and Leiomyosarcoma (5.0%, 3.4% and 3.4%, respectively). CONCLUSION: Our results reported the genetic landscape of HRR genes in Chinese sarcoma patients, providing a reference for the clinical application of PARP inhibitors. Citation Format: Feng Gao, Xuejiao Liu, Xiaojuan Wang, Chunyang Wang, Tonghui Ma, Changsheng Yang. Mutation profiling of homologous recombination-related (HRR) genes in sarcoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5755.