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. Methods and Findings: 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. © 2008 Paulson et al.
Paulson, T. G., Galipeau, P. C., Xu, L., Kissel, H. D., Li, X., Blount, P. L., … Reid, B. J. (2008). P16 mutation spectrum in the premalignant condition Barrett’s esophagus. PLoS ONE, 3(11). https://doi.org/10.1371/journal.pone.0003809