Prevalence of deleterious ATM germline mutations in gastric cancer patients.
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.
Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.|Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China.
Dong-Sheng
DS
Huang
Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.|Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China.
Hou-Quan
HQ
Tao
Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China.
Xu-Jun
XJ
He
Department of Surgery, No.2 Hospital of Deyang City, Deyang, Sichuan, China.
Ming
M
Long
Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China.
Sheng
S
Yu
Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China.
Ying-Jie
YJ
Xia
Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
Zhang
Z
Wei
Genetron Health (Beijing) Technology, Co. Ltd., Changping, Beijing, China.
Zikai
Z
Xiong
Personal Genome Diagnostics, Baltimore, MD, USA.
Sian
S
Jones
The Preston Robert Tisch Brain Tumor Center at Duke, and Department of Pathology, Duke University Medical Center, Durham, NC, USA.
Yiping
Y
He
Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China.|The Preston Robert Tisch Brain Tumor Center at Duke, and Department of Pathology, Duke University Medical Center, Durham, NC, USA.
Hai
H
Yan
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Xiaoyue
X
Wang
D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D001483:Base Sequence; D005192:Family Health; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics*
C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
ATM; cancer susceptibility; familial gastric cancer; hereditary cancer gene panel