Alterations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) are found frequently in human colorectal tumours displaying either microsatellite stability (MSS) or instability (MSI).
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.
Brueckl
Wolfgang M
WM
Department of Internal Medicine I, Friedrich-Alexander University Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. wbrueckl@molmed.uni-erlangen.de
Grombach
Jens
J
Wein
Axel
A
Ruckert
Stefan
S
Porzner
Marc
M
Dietmaier
Wolfgang
W
Rümmele
Petra
P
Croner
Roland S
RS
Boxberger
Frank
F
Kirchner
Thomas
T
Hohenberger
Werner
W
Hahn
Eckhart G
EG
Jung
Andreas
A
D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D016368:Frameshift Mutation; D006801:Humans; D018895:Microsatellite Repeats; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*
D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3