p16 mutation spectrum in the premalignant condition Barrett's esophagus

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. We have determined th...

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Bibliographic Details
Published in:PloS one 2008-11, Vol.3 (11), p.e3809-e3809
Main Authors: Paulson, Thomas G, Galipeau, Patricia C, Xu, Lianjun, Kissel, Heather D, Li, Xiaohong, Blount, Patricia L, Sanchez, Carissa A, Odze, Robert D, Reid, Brian J
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adult
Aged
Aged, 80 and over
Barrett Esophagus - genetics
Barrett's esophagus
Biology
Biopsy
Cell cycle
Clone Cells
Cohort Studies
Cyclin-dependent kinase inhibitors
Development and progression
DNA Mutational Analysis
Endoscopy
Epigenetics
Esophageal cancer
Esophagus
Esophagus - pathology
Exons
Female
Gastroenterology and Hepatology/Esophagus
Gastroesophageal reflux
Genes
Genes, p16
Genetic aspects
Genetics and Genomics/Cancer Genetics
Health risk assessment
Health sciences
Health surveillance
Heterozygosity
Histology
Human subjects
Humans
INK4 protein
Kinases
Loss of heterozygosity
Male
Medical research
Middle Aged
Mutation
Oncology/Gastrointestinal Cancers
Patients
Precancerous Conditions - genetics
Public health
Surveillance
Tumor suppressor genes
Young Adult
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Summary: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. 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. The results of this study suggest the environment of the esophagus in BE patients can both generate and select for clones with p16 mutations.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0003809