title: 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).
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.
authors.affiliation: Department of Internal Medicine I, Friedrich-Alexander University Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. wbrueckl@molmed.uni-erlangen.de
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Brueckl
authors.forename: Jens
authors.initials: J
authors.lastname: Grombach
authors.forename: Axel
authors.initials: A
authors.lastname: Wein
authors.forename: Stefan
authors.initials: S
authors.lastname: Ruckert
authors.forename: Marc
authors.initials: M
authors.lastname: Porzner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Petra
authors.initials: P
authors.lastname: Rümmele
authors.forename: Roland S
authors.initials: RS
authors.lastname: Croner
authors.forename: Frank
authors.initials: F
authors.lastname: Boxberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
authors.forename: Eckhart G
authors.initials: EG
authors.lastname: Hahn
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
mesh_terms: 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*
chemical_list: D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3