title: p16 mutation spectrum in the premalignant condition Barrett's esophagus.
abstract: BACKGROUND
  Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions.
  
  
  RESULTS
  We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett's esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma. Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation. The percentage of patients with p16 mutations increased with increasing histologic grade. In addition, samples from 3 out of 19 patients (15.8%) who underwent esophagectomy were found to have mutations.
  
  
  CONCLUSIONS
  The results of this study suggest the environment of the esophagus in BE patients can both generate and select for clones with p16 mutations.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. tpaulson@fhcrc.org
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Paulson
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Galipeau
authors.forename: Lianjun
authors.initials: L
authors.lastname: Xu
authors.forename: Heather D
authors.initials: HD
authors.lastname: Kissel
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Blount
authors.forename: Carissa A
authors.initials: CA
authors.lastname: Sanchez
authors.forename: Robert D
authors.initials: RD
authors.lastname: Odze
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000235:genetics*; D002999:Clone Cells; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004947:Esophagus / Q000473:pathology; D005091:Exons; D005260:Female; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics*; D055815:Young Adult