p16 expression in Barrett's esophagus and esophageal adenocarcinoma: association with genetic and epigenetic alterations
| Autor: | Alan G. Casson, S. Jane Darnton, Christopher P. Wild, Anita Chauhan, Yvonne L. Wallis, Pierre Hainaut, Laura J. Hardie |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Esophageal Neoplasms Tumor suppressor gene Adenocarcinoma Epigenesis Genetic Lesion Barrett Esophagus medicine Humans RNA Messenger Epigenetics Promoter Regions Genetic Cyclin-Dependent Kinase Inhibitor p16 Reverse Transcriptase Polymerase Chain Reaction business.industry Methylation DNA Methylation medicine.disease Immunohistochemistry digestive system diseases Epithelium medicine.anatomical_structure Oncology Barrett's esophagus DNA methylation medicine.symptom business |
| Zdroj: | Cancer Letters. 217:221-230 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2004.06.025 |
| Popis: | Alteration of the p16 tumor suppressor gene has been implicated as a critical lesion in the molecular pathogenesis of esophageal adenocarcinoma. The aim of this study was to characterize the spectrum of p16 alterations in surgically resected esophageal tissues, comprising histologically normal esophageal squamous and gastric epithelia, premalignant Barrett's epithelia, and associated esophageal adenocarcinomas, and to explore associations between p16 mRNA expression and p16 mutations, deletions, promoter hypermethylation, p16 protein expression, and clinico-pathologic features for the same tissues. We have shown that while p16 mutations are uncommon (2%; 1/54), hypermethylation of the p16 promoter is detected in 43% (9/21) of histologically normal epithelia, in 77% (14/18) of associated Barrett's epithelia, and in 85% (18/21) of esophageal adenocarcinomas. However, p16 mRNA levels (relative to matched normal epithelia) were variable in Barrett's epithelia and adenocarcinomas, having no clear correlation with methylation status or other molecular and clinico-pathological parameters. These findings are consistent with a role for the p16 tumor suppressor gene early in the molecular progression of Barrett's epithelium to invasive esophageal adenocarcinoma, but do not support the notion that the detection of hypermethylation is systematically associated with low levels of expression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect