INK4a-ARF alterations in Barrett?s epithelium, intraepithelial neoplasia and Barrett?s adenocarcinoma

Abstract

We conclude that most Barrett's intraepithelial neoplasms contain genetic and/or epigenetic INK4a-ARF alterations. Methylation of p16INK4a appears to be the most frequent epigenetic defect in the neoplastic progression of Barrett's tumourigenesis.

Increased phosphorylation on residue S795 of the retinoblastoma protein in esophageal adenocarcinoma

“…The discrepancy of gains of the P16 locus seen in one EAC cell line combined with a lower P16 protein expression, is likely due to hypermethylation of the p16 gene promoter. A process frequently observed in EAC (17,18,20). We further found an inverse correlation between P16 expression and phosphorylation of Rb forms in EAC cell lines and biopsies (Figs.…”

“…This aberrant phosphorylation of Rb is likely due to aberrations of its upstream regulator, the p16. Aberrant p16 as detected through methylation, loss of heterozygosity and immunohistochemistry has been frequently observed in EAC pathogenesis (17)(18)(19)(20). P16 has thus been a molecule of interest in EAC.…”

“…Aberrancy of p16, such as mutations, methylations and deletions, are some of the earliest events in cancer (16). P16 is also involved in the pathogenesis of EAC with a number of P16 alterations such as gene locus loss, LOH (loss of heterozygosity), mutations and methylation being present in BE, the pre-malignant stage of EAC (17)(18)(19)(20) and consequently increasing with increasing tissue dysplasia (17,18,20). In a number of cancers it has been shown that aberration of p16 affect phosphorylation status of Rb (21,22).…”

Molecular Markers in Mucosa Harboring Gastric Adenomas

“…The p16 INK4a gene is located in the chromosome 9p21 and is involved with the regulation of the cellular cycle (28) . The p16 INK4a gene is inactivated by mutations, homozigotics deletions, or metilation in diverse tumors of different origins and these metilation can result in deregulation of the cellular cycle (29) .…”

Gastroesophageal Reflux Disease: Molecular Predictors in Neoplastic Progression of Barrett's Esophagus

“…There exists an increasing amount of evidence showing that p16 inactivation is a critical step in the development of EAC. In fact the most prevalent genetic alteration in BE is the result of INK4A/CDKN2A hypermethylation, which is an early epigenetic change that occurs in the progression from BE to EAC (Bian et al, 2002;Hardie et al, 2005;Powell et al, 2005;Souza et al, 2001;Vieth et al, 2004).…”