Prevalence of deleterious ATM germline mutations in gastric cancer patients

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Base Sequence
  • Family Health
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Germ-Line Mutation*
  • Humans
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Pedigree
  • Sequence Analysis, DNA
  • Stomach Neoplasms / genetics*

Substances

  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins