title: Recombination phenotypes of the NCI-60 collection of human cancer cells.
abstract: BACKGROUND
  The NCI-60 is a collection of tumor cell lines derived from a variety of human adult cancer tissue types and is commonly used for genetic analysis and screening of potential chemotherapeutic agents. We wanted to understand the contributions of specific mechanisms of genomic instability to the etiology of cancers represented by the NCI-60.
  
  
  RESULTS
  We screened the NCI-60 for dysregulated homologous recombination by using the gene cluster instability (GCI) assay we pioneered, and for defects in base excision repair by sensitivity to 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). We identified subsets of the NCI-60 lines that either displayed the characteristic molecular signature of GCI or were sensitive to hmdUrd. With the exception of the NCI-H23 lung cancer line, these phenotypes were not found to overlap. None of the lines examined in either subset exhibited significant changes in the frequency of sister chromatid exchanges (SCE), neither did any of the lines in either subset exhibit microsatellite instability (MSI) indicative of defects in DNA mismatch repair.
  
  
  CONCLUSIONS
  Gene cluster instability, sensitivity to hmdUrd and sister chromatid exchange are mechanistically distinct phenomena. Genomic instability in the NCI-60 appears to involve only one mechanism of instability for each individual cell line.
authors.affiliation: Department of Toxicology, University of Kentucky, Lexington, KY, USA.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Stults
authors.forename: Michael W
authors.initials: MW
authors.lastname: Killen
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Shelton
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pierce
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004260:DNA Repair; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D005810:Multigene Family; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010641:Phenotype; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange; D013936:Thymidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C018080:5-hydroxymethyl-2'-deoxyuridine; D013936:Thymidine