title: Distinct methylation pattern and microsatellite instability in sporadic gastric cancer.
abstract: Aberrant 5' CpG island methylation is an alternative mechanism of gene inactivation during the development of cancer as demonstrated for several tumor-suppressor genes. Also, marked relationship of microsatellite instability (MSI) and DNA methylation has been reported in sporadic colorectal cancer, which is a result of epigenetic inactivation of hMLH1 in association of promoter hypermethylation. In the present study, we investigated the 5' CpG island hypermethylation of hMLH1, E-cadherin and p16 in 61 primary gastric cancers (GCs) by using combined bisulfite restriction analysis (COBRA) and methylation-specific PCR (MSP), and their MSI status. Of 61 GCs investigated, 5 (8.1%) tumors presented hMLH1 methylation, 16 (26.2%) and 25 (40.9%) showed E-cadherin and p16 methylation respectively, and 8 (13.1%) presented high-frequency MSI (MSI-H). Of the 8 MSI-H patients, 5 presented hMLH1 methylation, whereas no low-frequency MSI (MSI-L) and microsatellite stable (MSS) cases exhibited hMLH1 methylation (5/8 vs. 0/43, p < 0.00001). Furthermore, these patients also presented E-cadherin and p16 hypermethylation. Our data showed a significant correlation between hMLH1 methylation and MSI in GC, and suggested that a common mechanism of aberrant de novo methylation can be postulated in these cancers.
authors.affiliation: First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: F
authors.initials: F
authors.lastname: Itoh
authors.forename: M
authors.initials: M
authors.lastname: Toyota
authors.forename: T
authors.initials: T
authors.lastname: Kikuchi
authors.forename: H
authors.initials: H
authors.lastname: Kakiuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Hinoda
authors.forename: K
authors.initials: K
authors.lastname: Imai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins / Q000235:genetics; D002352:Carrier Proteins; D018899:CpG Islands; D019175:DNA Methylation; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D006801:Humans; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D013274:Stomach Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1