Frequent methylation of eyes absent 4 gene in Barrett's esophagus and esophageal adenocarcinoma
| Autor: | Kristie K. Klatt, Lawrence J. Burgart, David A. Ahlquist, Hongzhi Zou, Neal K. Osborn, Jonathan J. Harrington, Julian R. Molina |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Esophageal Neoplasms Epidemiology Biology Adenocarcinoma medicine.disease_cause Methylation Barrett Esophagus Metaplasia medicine Biomarkers Tumor Humans Esophagus Aged Aged 80 and over Esophageal disease Cancer Esophageal cancer Middle Aged medicine.disease digestive system diseases medicine.anatomical_structure Oncology Barrett's esophagus DNA methylation Cancer research Trans-Activators Female medicine.symptom Carcinogenesis |
| Zdroj: | Cancer epidemiology, biomarkersprevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 14(4) |
| ISSN: | 1055-9965 |
| Popis: | Most esophageal adenocarcinomas arise within Barrett's esophagus but the cause of this increasingly prevalent condition remains unknown. Early detection improves survival and discriminant screening markers for Barrett's esophagus and cancer are needed. This study was designed to explore the natural history of eyes absent 4 (EYA4) gene methylation in the neoplastic progression of Barrett's esophagus and to evaluate methylated EYA4 as a candidate marker. Aberrant promoter methylation of EYA4 was studied by methylation-specific PCR using bisulfite-treated DNA from esophageal adenocarcinomas, Barrett's esophagus, and normal epithelia, and then confirmed by sequencing. Eight cancer cell lines were treated with the demethylation agent 5-aza-2′-deoxycytidine, and EYA4 mRNA expression with and without treatment was quantified by real-time reverse-transcription PCR. EYA4 hypermethylation was detected in 83% (33 of 40) of esophageal adenocarcinomas and 77% (27 of 35) of Barrett's tissues, but only in 3% (2 of 58) of normal esophageal and gastric mucosa samples (P < 0.001). The unmethylated cancer cell lines had much higher EYA4 mRNA expression than the methylated cancer cell lines. Demethylation caused by 5-aza-2′-deoxycytidine increased the mRNA expression level by a median of 3.2-fold in methylated cells, but its effect on unmethylated cells was negligible. Results indicate that aberrant promoter methylation of EYA4 is very common during tumorigenesis in Barrett's esophagus, occurs in early metaplasia, seems to be an important mechanism of down-regulating EYA4 expression, and represents an intriguing candidate marker for Barrett's metaplasia and esophageal cancer. |
| Databáze: | OpenAIRE |
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