Aberrant vimentin methylation is characteristic of upper gastrointestinal pathologies.
Abstract
We have previously established aberrant DNA methylation of vimentin exon-1 (VIM methylation) as a common epigenetic event in colon cancer and as a biomarker for detecting colon neoplasia. We now examine vimentin methylation in neoplasia of the upper gastrointestinal tract.
Using a quantitative real-time methylation-specific PCR assay, we tested for vimentin methylation in archival specimens of esophageal and gastric neoplasia.
We find that acquisition of aberrant vimentin methylation is highly common in these neoplasms, but largely absent in controls. The highest frequency of vimentin methylation was detected in lesions of the distal esophagus, including 91% of Barrett's esophagus (n = 11), 100% of high-grade dysplasia (HGD, n = 5), and 81% of esophageal adenocarcinoma (EAC, n = 26) but absent in controls (n = 9). Vimentin methylation similarly was detected in 87% of signet ring (n = 15) and 53% of intestinal type gastric cancers (n = 17). Moreover, in tests of cytology brushings vimentin methylation proved detectable in 100% of Barrett's esophagus cases (n = 7), 100% of HGD cases (n = 4), and 83% of EAC cases (n = 18) but was absent in all controls (n = 5).
These findings establish aberrant vimentin methylation as a highly common epigenetic alteration in neoplasia of the upper gastrointestinal tract and show that Barrett's esophagus, even without dysplasia, already contains epigenetic alterations characteristic of adenocarcinoma.
These findings suggest vimentin methylation as a biomarker of upper gastrointestinal neoplasia with potential for development as molecular cytology in esophageal screening.
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Authors
- Barnholtz-Sloan JS
- Chak A
- Chen Y
- Leidner RS
- Lutterbaugh J
- Markowitz SD
- Moinova H
- Ravi L
- Willis JE