title: Increased frequency of CpG island methylator phenotype and CDH1 methylation in a gastric cancer high-risk region of china.
abstract: This study aimed to profile the methylation statuses of CDH1/E-cadherin and five CpG island methylator phenotype (CIMP)-associated genes (p16, hMLH1, MINT1, MINT2, and MINT31) in gastric specimens of 47 Dalian long-term residents with and 31 without gastric cancers (GCs). CIMP patterns were classified as CIMP-H with over three methylated genes, CIMP-L with one to two methylated genes, and CIMP-N without methylation. Of 47 GC cases, 24 (51.1%) were CIMP-H, 18 (38.3%) were CIMP-L, and 5 (10.6%) were CIMP-N, whereas 5 of 21 (23.8%) premalignant lesions were CIMP-H and 15 (71.4%) were CIMP-L. CIMP-L was found in 75% (12/16) of GC-adjacent mucosa and in 38.7% (12/31) of mucosa from GC-free patients. CDH1 methylation occurred in 48.9% (23/47) of cancer, in 23.8% (5/21) of premalignant, and in 25% (4/16) of noncancerous tissues and was correlated with patients' age (P = .01), lymph node metastasis, and CIMP severity (P = .000-.028). Our results demonstrated that the frequencies of CIMP-H in Dalian GCs, CIMP-L, and p16 methylation in GC-adjacent tissues and in GC-free mucosa were much higher than those reported previously, indicating the elevated methylation pressure in this GC high-risk region. The close correlation between CDH1 methylation and CIMP severity suggests the necessity of their combination in GC prevention and earlier diagnosis.
authors.affiliation: Department of Cell Biology and Liaoning Laboratory of Cancer Genomics, College of Basic Medical Sciences, Dalian Medical University, Dalian 116027, PR China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Qu
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Cui
authors.forename: Qing-You
authors.initials: QY
authors.lastname: Kong
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Liu