Original articleAberrant Methylation of the Eyes Absent 4 Gene in Ulcerative Colitis–Associated Dysplasia
Section snippets
Materials and Methods
This study was approved by the Mayo Clinic Institutional Review Board and by an external Institutional Review Board for participating sites.
Bisulfite Genomic Sequencing
EYA4 promoter methylation of colorectal tissues was confirmed by bisulfite sequencing. There were significant differences in all analyzed sequences between the cancers and adjacent normal tissues (P < .03, all rows; Figure 1). Overall, 80% (8 of 10) of the cancers and none (0 of 9) of the adjacent normal tissues showed promoter hypermethylation of the EYA4 gene.
EYA4 and hMLH1 Methylation in Noncolitic Tissues
The difference in EYA4 methylation was statistically significant between cancer and normal tissues, and between neoplasia (cancer and
Discussion
In ulcerative colitis, surveillance strategies for colorectal cancer prevention would be strengthened by the addition of accurate markers for dysplasia. The EYA4 methylation marker evaluated in this tissue study highly discriminated cancer and dysplasia from nonneoplasia controls and merits further consideration.
In CUC tissues, the EYA4 methylation assay detected more than 80% of neoplastic lesions while retaining a specificity of 100%. This impressive specificity was noted in 2 separate
References (23)
- et al.
Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis
Gastroenterology
(1994) - et al.
Histopathological and clinical evaluation of serrated adenomas of the colon and rectum
Mod Pathol
(2003) - et al.
The relationship between hypomethylation and CpG island methylation in colorectal neoplasia
Am J Pathol
(2003) - et al.
Stool screening for colorectal cancermolecular approaches
Gastroenterology
(2005) - et al.
Methylation changes in faecal DNAa marker for colorectal cancer screening?
Lancet
(2004) - et al.
Analysis of promoter methylation in stoola novel method for the detection of colorectal cancer
Clin Gastroenterol Hepatol
(2005) - et al.
Misexpression of the Eyes Absent family triggers the apoptotic program
J Biol Chem
(2002) - et al.
Surveillance issues in inflammatory bowel diseaseulcerative colitis
J Clin Gastroenterol
(2001) - et al.
Ulcerative colitis-associated neoplasia
Pathol Int
(2002) - et al.
Hypermethylation of the p16INK4a promoter in colectomy specimens of patients with long-standing and extensive ulcerative colitis
Cancer Res
(1998)
Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1
Cancer Res
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Supported by a generous grant from Charles Oswald.
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Joern Lewin is employed by Epigenomics AG, Berlin, Germany, and Ralf Lesche and Cathy Lofton-Day are employed by Epigenomics Inc, Seattle, Washington.