title: DNA methylation profiles of differentiated-type gastric carcinomas with distinct mucin phenotypes.
abstract: Gastric carcinomas (GC) are classified into four phenotypes according to mucin expression. Previous studies revealed the association of distinct genetic profiles in GC with mucin phenotypic expression; however, the roles of epigenetic changes, such as DNA methylation, are poorly understood. We examined whether the phenotypic expression of GC was associated with DNA methylation of hMLH1, MGMT, p16(INK4a), RAR-beta or CDH1. Expression of HGM, M-GGMC-1, MUC2, and CD10 was analyzed immunohistochemically in 33 advanced GC with differentiated histology. HGM was expressed in 14 (42.4%) cases, M-GGMC-1 in five (15.2%) cases, MUC2 in 15 (45.5%) cases and CD10 in 18 (54.5%) cases. DNA methylation was detected in five (15.2%) cases for hMLH1, 11 (33.3%) cases for MGMT, 13 (39.4%) cases for p16(INK4a), 17 (51.5%) cases for RAR-beta and 14 (42.4%) cases for CDH1 by bisulfite-polymerase chain reaction and methylation-specific polymerase chain reaction. DNA methylation of hMLH1 occurred more frequently in MUC2-negative GC than in MUC2-positive GC (P = 0.0488, Fisher's exact test). In contrast, MGMT was more frequently methylated in MUC2-positive GC than in MUC2-negative GC (P = 0.0078, Fisher's exact test). There was no correlation between gastric or intestinal-markers and methylation of the p16(INK4a), RAR-beta and CDH1 genes. These results indicate that DNA methylation of specific genes, such as hMLH1 and MGMT, may be involved partly in the distinct phenotypic expression of GC.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Motoshita
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kuraoka
authors.forename: Phyu Phyu
authors.initials: PP
authors.lastname: Aung
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Taniyama
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsusaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020869:Gene Expression Profiling; D006801:Humans; D009077:Mucins / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D018168:Receptors, Retinoic Acid / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009077:Mucins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D000070957:MutL Protein Homolog 1