title: Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer.
abstract: Hereditary Non-Polyposis Colon Cancer (HNPCC) tumors and some sporadic colon cancers acquire somatic changes in the length of microsatellite sequences. We hypothesized that this 'replication error' (RER) phenotype in these cancers reflects a more general defect which should result in hypermutability of expressed genes. To test this hypothesis mutations of hprt were studied in RER and non-RER tumor cell lines. Increased mutation rates of greater than 100-fold were found in RER compared to non-RER lines. Heterogeneity within the RER group suggests the likely existence of different classes of RER tumors. One non-RER cell line demonstrated a greater than 10-fold increase in mutation rate, suggesting that a novel mutator phenotype may exist in some non-RER tumors.
authors: Department of Pathology, University Hospitals of Cleveland, Ohio.
authors: J R
authors: JR
authors: Eshleman
authors: E Z
authors: EZ
authors: Lang
authors: G K
authors: GK
authors: Bowerfind
authors: R
authors: R
authors: Parsons
authors: B
authors: B
authors: Vogelstein
authors: J K
authors: JK
authors: Willson
authors: M L
authors: ML
authors: Veigl
authors: W D
authors: WD
authors: Sedwick
authors: S D
authors: SD
authors: Markowitz
mesh_terms: D002455:Cell Division / Q000187:drug effects; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004276:DNA, Satellite / Q000235:genetics*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D009154:Mutation; D013866:Thioguanine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D004276:DNA, Satellite; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine