title: Molecular analysis of mutations in mutator colorectal carcinoma cell lines.
abstract: The nature of mutations occurring in two colorectal carcinoma cell lines deficient in mismatch repair and displaying mutator phenotypes was determined. One of the lines (HCT116) exhibited a higher level of microsatellite instability than the second (DLD-1), although the rate of mutation at the selectable locus encoding the purine salvage enzyme hypoxanthine guanine phosphoribosyl transferase (HPRT) was equally elevated (about 350-450-fold relative to mismatch repair proficient cell lines). Transitions were the major class of mutations in the two mutator lines. In DLD-1 these mutations recurred at several sites that appeared to be hotspots. Frameshifts at a run of six guanine residues in the coding sequence for HPRT constituted 35% of mutations in HCT116. These frameshifts were highly unstable and reverted to wild type at high frequency. Larger deletions were also detected in HCT116. Although these deletions constituted a small proportion of mutations compared with the other types, our data suggest that the rate of deletion is elevated relative to mismatch repair proficient (hMLH1+) cell lines. These observations suggest that the gene(s) altered in DLD-1 may preferentially affect the repair of base mismatches while the alteration(s) in HCT116 may affect the repair of both mismatches and frameshifts.
authors.affiliation: Department of Radiation Oncology, Eccles Institute of Human Genetics, University of Utah, Salt Lake City 84112, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Bhattacharyya
authors.forename: A
authors.initials: A
authors.lastname: Ganesh
authors.forename: G
authors.initials: G
authors.lastname: Phear
authors.forename: B
authors.initials: B
authors.lastname: Richards
authors.forename: A
authors.initials: A
authors.lastname: Skandalis
authors.forename: M
authors.initials: M
authors.lastname: Meuth
mesh_terms: D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm; D004276:DNA, Satellite / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D004276:DNA, Satellite; D007041:Hypoxanthine Phosphoribosyltransferase