title: Integrated analysis of cancer-related pathways affected by genetic and epigenetic alterations in gastric cancer.
abstract: BACKGROUND
  The profiles of genetic and epigenetic alterations in cancer-related pathways are considered to be useful for selection of patients likely to respond to specific drugs, including molecular-targeted and epigenetic drugs. In this study, we aimed to characterize such profiles in gastric cancers (GCs).
  
  
  METHODS
  Genetic alterations of 55 cancer-related genes were analyzed by a benchtop next-generation sequencer. DNA methylation statuses were analyzed by a bead array with 485,512 probes.
  
  
  RESULTS
  The WNT pathway was activated by mutations of CTNNB1 in 2 GCs and potentially by aberrant methylation of its negative regulators, such as DKK3, NKD1, and SFRP1, in 49 GCs. The AKT/mTOR pathway was activated by mutations of PIK3CA and PTPN11 in 4 GCs. The MAPK pathway was activated by mutations and gene amplifications of ERBB2, FLT3, and KRAS in 11 GCs. Cell-cycle regulation was affected by aberrant methylation of CDKN2A and CHFR in 13 GCs. Mismatch repair was affected by a mutation of MLH1 in 1 GC and by aberrant methylation of MLH1 in 2 GCs. The p53 pathway was inactivated by mutations of TP53 in 19 GCs and potentially by aberrant methylation of its downstream genes in 38 GCs. Cell adhesion was affected by mutations of CDH1 in 2 GCs.
  
  
  CONCLUSIONS
  Genes involved in cancer-related pathways were more frequently affected by epigenetic alterations than by genetic alterations. The profiles of genetic and epigenetic alterations are expected to be useful for selection of the patients who are likely to benefit from specific drugs.
authors: Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
authors: Yukie
authors: Y
authors: Yoda
authors: Hideyuki
authors: H
authors: Takeshima
authors: Tohru
authors: T
authors: Niwa
authors: Jeong Goo
authors: JG
authors: Kim
authors: Takayuki
authors: T
authors: Ando
authors: Ryoji
authors: R
authors: Kushima
authors: Toshiro
authors: T
authors: Sugiyama
authors: Hitoshi
authors: H
authors: Katai
authors: Hirokazu
authors: H
authors: Noshiro
authors: Toshikazu
authors: T
authors: Ushijima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases