Mutation profiling of mismatch repair-deficient colorectal cncers using an in silico genome scan to identify coding microsatellites.
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.
Park
Jane
J
Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Laboratory Medicine University of Toronto, Toronto, Ontario, Canada M5G 1X5.
Betel
Doron
D
Gryfe
Robert
R
Michalickova
Katerina
K
Di Nicola
Nando
N
Gallinger
Steven
S
Hogue
Christopher W V
CW
Redston
Mark
M
D000465:Algorithms; D020137:Base Pair Mismatch; D015179:Colorectal Neoplasms / Q000235:genetics*; D019295:Computational Biology; D004260:DNA Repair; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation