Abstract 805: A germline mutation of gene ATM p.C1899* is associated with a family history of multiple cancers in a family in Yunnan province, China

Abstract

Abstract Background: Ataxia-telangiectasia mutated (ATM) is a gene that plays role in cell cycle checkpoints and DNA damage response, heterozygous germline mutations in ATM are considered as one of risk factor of breast cancer (BC). There are also some reports that ATM mutations are related to other tumor types, such as prostate cancer. Several pathogenic germline mutations in ATM have been reported included missense mutations, nonsense mutations, frameshift deletions, in-frame deletion, large deletion. Here, we report a family history of multiple cancers related to germline mutation of ATM p.C1899* in a family in Yunnan province, China. Methods: The proband is a 58-year old male patient with colon cancer. Both tumor tissue samples and peripheral blood sample of the proband was subjected to next generation sequencing (NGS) analysis by 3D Medicines Inc., Shanghai, China, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). A novel germ-line mutation was identified, that was heterozygous ATM p.C1899* mutation (c.5697C>A). Peripheral blood sample of other family members have been collected and send to 3D Medicines Inc., for NGS analysis. Results: In total of 6 members of the family underwent NGS analysis, results showed that these members were carry a germline mutation of gene ATM p.C1899*, one uncle was patient with gastric cancer, and one aunt was patient with pancreatic cancer, which means this germline mutation was related with three different cancer in a family. Conclusion: The mutation of ATM, especially germline mutation, may associated with multiple cancers, such as gastric cancer, colorectal cancer and pancreatic cancer. Accurate genetic testing should be given more attention to better control the risk of familial cancer. Citation Format: Xianghua Sun, Hushan Zhang, Wanfu Zhang, Zhiping Zhang, Bo Li. A germline mutation of gene ATM p.C1899* is associated with a family history of multiple cancers in a family in Yunnan province, China [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 805.