title: MINT31 methylation in gastric noninvasive neoplasia:  potential role in the secondary prevention of gastric cancer.
abstract: Gastric cancer (GC) is still a leading cause of cancer-related death worldwide, and environmental, genetic, and epigenetic DNA changes are involved in the process of gastric carcinogenesis. The objective of this study was to establish the extent of DNA methylation at various CpG islands in GC and in precancerous changes [gastric noninvasive neoplasia (NIN)]. Eighty-one gastric samples were analyzed using methylation-specific PCR at several CpG islands. Thirty-eight samples were obtained at surgery [19 neoplastic (GC) and 19 nonneoplastic cancer-surrounding tissues (sGC)] and 43 at endoscopy (biopsies in 23 NIN patients and 20 controls). Hypermethylation of TPEF (a growth inhibitor), PTGER3 (a prostaglandin receptor isoform), and MINT31 (a promoter locus regulating calcium channels that is involved in p53 mutation) discriminated NIN and GC from normal mucosa, suggesting an early role as initiating events, whereas hypermethylation at ARGHAP20 developed with the progression from NIN to GC. MINT31 hypermethylation predicted persistence or worsening of NIN and cancer development. In conclusion, these data support a progressive accumulation of aberrant methylations in NIN and GC at various CpG islands with distinct time courses. With hypermethylation, the genes involved in regulating the balance between apoptosis and cell proliferation may become silenced and trigger gastric tumorigenesis. Hypermethylation of MINT31 predicted NIN persistence, as well as progression to higher grade or to GC, and might be used as a marker of GC risk.
authors.affiliation: Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Elena
authors.initials: E
authors.lastname: Miotto
authors.forename: Silvia
authors.initials: S
authors.lastname: Sabbioni
authors.forename: Romilda
authors.initials: R
authors.lastname: Cardin
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.forename: Chiara
authors.initials: C
authors.lastname: Tieppo
authors.forename: Marika
authors.initials: M
authors.lastname: Piciocchi
authors.forename: Gemma
authors.initials: G
authors.lastname: Maddalo
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D005260:Female; D005500:Follow-Up Studies; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D055502:Secondary Prevention; D013274:Stomach Neoplasms / Q000473:pathology / Q000517:prevention & control*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C476510:SPEN protein, human