home > bioproject > PRJDB1840
identifier PRJDB1840
type bioproject
sameAs
sra-study  DRP001077
organism Homo sapiens
title Mutation profiles in inflamed gastric epithelium with Helicobacter pylori infection during the development of gastric cancer.
description Helicobacter pylori (H. pylori) infection and the resultant chronic gastric inflammation is an important etiologic factor for gastric cancer development. To explore the genetic basis of gastric cancer that developed in the inflamed gastric mucosa, we investigated genetic aberrations latently accumulated in non-tumorous chronically inflamed gastric epithelium. Whole exome sequencing on 5 matched pairs of gastric cancer and non-cancerous gastritis tissues in patients with H. pylori infection clarified that somatic mutations were accumulated in various genes in inflamed gastric tissues. Additional deep sequencing analyses on the tumor-related genes including TP53, ARID1A, CTNNB1, PIK3CA, MLL2 and SUV39H1 were performed in H. pylori-related gastritis mucosa in 23 patients with gastric cancer and 6 patients without gastric cancer. By deep sequencing, non-synonymous mutations on gastritis mucosa of 23 patients with gastric cancer were detected in TP53 in 9 cases (39.1%), ARID1A in 2 cases (8.7%), and MLL2 in 2 cases (8.7%), as well as non-synonymous mutations on gastritis mucosa of patients without gastric cancer were detected in TP53 in 4 cases (66.7%) and ARID1A in 1 cases (16.7%). Interestingly, not only mutations in gastric cancer genomes but also TP53 mutations in H. pylori-inflamed gastritis mucosa were predominantly C:G>T:A transitions in the context of GpCpX or ApCpX, mutation signatures invloved in activation-induced cytidine deaminase (AID) activity. Furthermore, in vivo studies with human TP53 knocked-in mice model revealed that constitutive AID expression in gastric mucosa caused the generation of TP53 mutations whose positions were hot spots in human gastric cancers. These findings provide novel evidence that somatic mutations were latently accumulated in various genes in inflamed gastric mucosa with H. pylori infection. The genetic alterations accumulated in TP53 gene of the gastritis mucosa would provide a putative genetic basis for the increased susceptibility to gastric carcinogenesis in patients with H. pylori infection.
data type Other
external link
properties 
{...}
dbXrefs
sra-run  DRR013000DRR013001DRR013002DRR013003DRR013004DRR013005DRR013006DRR013007DRR013008DRR013009 More
sra-submission  DRA001035
biosample  SAMD00002733SAMD00002734SAMD00002742SAMD00002738SAMD00002747SAMD00002737SAMD00002743SAMD00002740SAMD00002745SAMD00002746 More
sra-study  DRP001077
sra-sample  DRS011732DRS011733DRS011734DRS011735DRS011736DRS011737DRS011738DRS011739DRS011740DRS011742 More
sra-experiment  DRX011890DRX011891DRX011892DRX011893DRX011894DRX011895DRX011896DRX011897DRX011898DRX011900 More
distribution JSONJSON-LD
status public
visibility unrestricted-access
dateCreated 2014-05-12T00:46:27+0000
dateModified 2014-11-10T00:02:00+0000
datePublished 2014-11-10T00:02:00+0000