title: Mutation profiling of mismatch repair-deficient colorectal cncers using an in silico genome scan to identify coding microsatellites.
abstract: Human colorectal, endometrial, and gastric cancers with defective DNA mismatch repair (MMR) have microsatellite instability, a unique molecular alteration characterized by widespread frameshift mutations of repetitive DNA sequences. We developed "Kangaroo," a bioinformatics program for searches in nucleotide and protein sequence databases, and performed an in silico genome scan for DNA coding microsatellites that may have novel mutations in MMR-deficient cancers. Examination of 29 previously untested coding polyadenines revealed widespread mutations in MMR-deficient colorectal cancers, with the highest frequencies in ERCC5, CASP8AP2, p72, RAD50, CDC25, RECQL1, CBF2, RACK7, GRK4, and DNAPK (range, 10-33%). This algorithm allows comprehensive mutation profiling of MMR-deficient cancers, an important step in understanding the pathogenesis of these neoplasms.
authors.affiliation: Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Laboratory Medicine University of Toronto, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Jane
authors.initials: J
authors.lastname: Park
authors.forename: Doron
authors.initials: D
authors.lastname: Betel
authors.forename: Robert
authors.initials: R
authors.lastname: Gryfe
authors.forename: Katerina
authors.initials: K
authors.lastname: Michalickova
authors.forename: Nando
authors.initials: N
authors.lastname: Di Nicola
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Christopher W V
authors.initials: CW
authors.lastname: Hogue
authors.forename: Mark
authors.initials: M
authors.lastname: Redston
mesh_terms: D000465:Algorithms; D020137:Base Pair Mismatch; D015179:Colorectal Neoplasms / Q000235:genetics*; D019295:Computational Biology; D004260:DNA Repair; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation