Author/Authors :
Tanja M. Brueckl، نويسنده , , Wolfgang M. and Grombach، نويسنده , , Jens and Wein، نويسنده , , Axel and Ruckert، نويسنده , , Stefan and Porzner، نويسنده , , Marc and Dietmaier، نويسنده , , Wolfgang and Rümmele، نويسنده , , Petra and Croner، نويسنده , , Roland S. and Boxberger، نويسنده , , Frank and Kirchner، نويسنده , , Thomas and Hohenberger، نويسنده , , Werner and Hahn، نويسنده , , Eckhart G. and Jung، نويسنده , , Andreas، نويسنده ,
Abstract :
Methylation of promoter regions and frameshift mutations in microsatellites of the coding sequence (CDS) of genes are frequently associated with loss of expression in microsatellite instable (MSI) colorectal carcinoma. In a panel of 40 MSI and 24 microsatellite stable (MSS) colorectal tumours as well as six cultured colorectal carcinoma cell lines hypermethylation of the TIMP3-promoter was found in 28% of MSI and 25% of MSS tumours, respectively. Additionally, three MSI tumours and one cell line displayed instability of a C7-repeat located in the CDS of the TIMP-3 gene. TIMP-3 fulfils all important criteria for being a target gene in the mutator pathway. Thus, TIMP-3 might be a factor of general importance for colorectal carcinogenesis.
Keywords :
Microsatellite instability (MSI) , Mismatch repair (MMR) deficiency , colorectal carcinoma , Tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) , Sorsby fundus dystrophy (SFD)
