title: Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers.
abstract: Recent development of personal sequencers for extensive mutation analysis and bead array technology for comprehensive DNA methylation analysis have made it possible to obtain integrated pictures of genetic and epigenetic alterations on the same set of cancer samples. Here, we aimed to establish such pictures of gastric cancers (GCs). Comprehensive methylation analysis of 30 GCs revealed that the number of aberrantly methylated genes was highly variable among individual GCs. Extensive mutation analysis of 55 known cancer-related genes revealed that 19 of the 30 GCs had 24 somatic mutations of eight different genes (CDH1, CTNNB1, ERBB2, KRAS, MLH1, PIK3CA, SMARCB1, and TP53). Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, CTNNB1, ERBB2, KRAS, and PIK3CA. This is one of the first studies in which both genetic and epigenetic alterations were extensively analyzed in the same set of samples. It was also demonstrated for the first time in GCs that the CIMP was associated with oncogene mutations.
authors.affiliation: Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Jeong Goo
authors.initials: JG
authors.lastname: Kim
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeshima
authors.forename: Tohru
authors.initials: T
authors.lastname: Niwa
authors.forename: Emil
authors.initials: E
authors.lastname: Rehnberg
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shigematsu
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yoda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
authors.forename: Takao
authors.initials: T
authors.lastname: Maekita
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Katai
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Young Seon
authors.initials: YS
authors.lastname: Hong
authors.forename: Cho Hyun
authors.initials: CH
authors.lastname: Park
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm