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Oncotarget. 2015 Dec 1;6(38):40953-8. doi: 10.18632/oncotarget.5944.

Prevalence of deleterious ATM germline mutations in gastric cancer patients.

Author information

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.

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.

KEYWORDS:

ATM; cancer susceptibility; familial gastric cancer; hereditary cancer gene panel

PMID:
26506520
PMCID:
PMC4747381
DOI:
10.18632/oncotarget.5944
[Indexed for MEDLINE]
Free PMC Article

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