title: Analysis of K-ras codon 12 mutation in flat and nodular variants of serrated adenoma in the colon.
abstract: OBJECTIVE
  The developmental process of serrated adenomas is obscure, and the importance of genetic alterations has not been elucidated clearly. The possibility that the developmental process and genetic alterations of serrated adenomas could differ from those of ordinary tubular adenomas was explored in this work.
  
  
  METHODS
  Serrated adenomas were obtained by endoscopic resection (n = 57) and divided into two groups: flat (n = 10) and nodular (n = 47). Mutation of the K-ras gene was analyzed by enriched polymerase chain reaction-enzyme-linked mini-sequence assay, which can detect not only the presence of a mutation but also the mutation type of K-ras codon 12 with high sensitivity. Methylation-specific polymerase chain reaction was performed with specific primers for the DNA repair gene O6-methylguanine-DNA methyltransferase.
  
  
  RESULTS
  Serrated adenomas located in the rectum were more likely to have a K-ras mutation (9/12, 75 percent), whereas serrated adenomas of the flat type were less likely to have one (1/10, 10 percent). Furthermore, nodular serrated adenomas that occurred in the rectum possessed a high frequency of K-ras gene codon 12 point mutation (8/10, 80 percent) despite an overall frequency of 46.8 percent (22/47). A mutation of the K-ras codon 12 gene was detected in 23 (40.4 percent) of 57 serrated adenomas. Three types of point mutations of codon 12 were detected, with the mutation of GAT being observed most frequently.
  
  
  CONCLUSIONS
  This study shows that development of nodular serrated adenomas may depend on the mutation of the K-ras codon 12 gene, whereas development of flat serrated adenomas may not. Additionally, serrated adenomas that occur in the rectum are closely related to the mutation of the K-ras codon 12 gene. K-ras mutations in serrated adenomas may be unaffected by the epigenetic silencing of O6-methylguanine-DNA methyltransferase by promoter hypermethylation.
authors.affiliation: First Department of Internal Medicine, Kochi Medical School, Kochi, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Higashidani
authors.forename: Satoru
authors.initials: S
authors.lastname: Tamura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Morita
authors.forename: Takehisa
authors.initials: T
authors.lastname: Tadokoro
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Seisho
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Taguchi
authors.forename: Saburo
authors.initials: S
authors.lastname: Onishi
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003062:Codon / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D003113:Colonoscopy; D004252:DNA Mutational Analysis; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D003062:Codon