TY  - JOUR
A1  - Gerecke, Christian
A1  - Scholtka, Bettina
A1  - Loewenstein, Yvonne
A1  - Fait, Isabel
A1  - Gottschalk, Uwe
A1  - Rogoll, Dorothee
A1  - Melcher, Ralph
A1  - Kleuser, Burkhard
T1  - Hypermethylation of ITGA4, TFPI2 and VIMENTIN promoters is increased in inflamed colon tissue: putative risk markers for colitis-associated cancer
JF  - Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft
N2  - Epigenetic silencing of tumor suppressor genes is involved in early transforming events and has a high impact on colorectal carcinogenesis. Likewise, colon cancers that derive from chronically inflamed bowel diseases frequently exhibit epigenetic changes. But there is little data about epigenetic aberrations causing colorectal cancer in chronically inflamed tissue. The aim of the present study was to evaluate the aberrant gain of methylation in the gene promoters of VIM, TFPI2 and ITGA4 as putative early markers in the development from inflamed tissue via precancerous lesions toward colorectal cancer.
 Initial screening of different cancer cell lines by using methylation-specific PCR revealed a putative colon cancer-specific methylation pattern. Additionally, a demethylation assay was performed to investigate the methylation-dependent gene silencing of ITGA4. The candidate markers were analyzed in colonic tissue specimens from patients with colorectal cancer (n = 15), adenomas (n = 76), serrated lesions (n = 13), chronic inflammation (n = 10) and normal mucosal samples (n = 9).
 A high methylation frequency of VIM (55.6 %) was observed in normal colon tissue, whereas ITGA4 and TFPI2 were completely unmethylated in controls. A significant gain of methylation frequency with progression of disease as well as an age-dependent effect was detectable for TFPI2. ITGA4 methylation frequency was high in precancerous and cancerous tissues as well as in inflammatory bowel diseases (IBD).
 The already established methylation marker VIM does not permit a specific and sensitive discrimination of healthy and neoplastic tissue. The methylation markers ITGA4 and TFPI2 seem to be suitable risk markers for inflammation-associated colon cancer.
KW  - Epigenetic
KW  - DNA methylation
KW  - Colon cancer
KW  - Colitis
KW  - Gastrointestinal tract
KW  - Biomarker
Y1  - 2015
U6  - https://doi.org/10.1007/s00432-015-1972-8
SN  - 0171-5216
SN  - 1432-1335
VL  - 141
IS  - 12
SP  - 2097
EP  - 2107
PB  - Springer
CY  - New York
ER  -