Open AccessPrevalence of deleterious ATM germline mutations in gastric cancer patients
Author(s) -
Dongsheng Huang,
HouQuan Tao,
Xujun He,
Ming Long,
Sheng Yu,
Yingjie Xia,
Zhang Wei,
Zikai Xiong,
Siân Jones,
Yiping He,
Hai Yan,
Xiaoyue Wang
Publication year - 2015
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.5944
Subject(s) - cancer , germline , germline mutation , genetic predisposition , medicine , exome sequencing , genetics , mutation , exome , genetic testing , cancer research , gene , oncology , biology
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.
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