Prevalence of deleterious ATM germline mutations in gastric cancer patients

// Dong-Sheng Huang 1,2,* , Hou-Quan Tao 1,2,* , Xu-Jun He 2 , Ming Long 3 , Sheng Yu 2 , Ying-Jie Xia 2 , Zhang Wei 1 , Zikai Xiong 4 , Sian Jones 5 , Yiping He 6 , Hai Yan 2,6 and Xiaoyue Wang 7 1 Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China 2 Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China 3 Department of Surgery, No.2 Hospital of Deyang City, Deyang, Sichuan, China 4 Genetron Health (Beijing) Technology, Co. Ltd., Changping, Beijing, China 5 Personal Genome Diagnostics, Baltimore, MD, USA 6 The Preston Robert Tisch Brain Tumor Center at Duke, and Department of Pathology, Duke University Medical Center, Durham, NC, USA 7 State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China * These authors have contributed equally to this work Correspondence to: Hou-Quan Tao, email: // Hai Yan, email: // Xiaoyue Wang, email: // Keywords : familial gastric cancer, ATM, cancer susceptibility, hereditary cancer gene panel Received : July 31, 2015 Accepted : September 12, 2015 Published : October 23, 2015 Abstract Besides CDH1 , few hereditary gastric cancer predisposition genes have been previously reported. In this study, we discovered two germline ATM mutations (p.Y1203fs and p.N1223S) in a Chinese family with a history of gastric cancer by screening 83 cancer susceptibility genes. Using a published exome sequencing dataset, we found deleterious germline mutations of ATM in 2.7% of 335 gastric cancer patients of different ethnic origins. The frequency of deleterious ATM mutations in gastric cancer patients is significantly higher than that in general population (p=0.0000435), suggesting an association of ATM mutations with gastric cancer predisposition. We also observed biallelic inactivation of ATM in tumors of two gastric cancer patients. Further evaluation of ATM mutations in hereditary gastric cancer will facilitate genetic testing and risk assessment.