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Genomic instability and target gene mutations in colon cancers with different degrees of allelic shifts
Author(s) -
Percesepe Antonio,
Pedroni Monica,
Sala Elisa,
Menigatti Mirco,
Borghi Francesca,
Losi Lorena,
Viel Alessandra,
Genuardi Maurizio,
Benatti Piero,
Roncucci Luca,
Peltomäki Päivi,
Ponz de Leon Maurizio
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(200004)27:4<424::aid-gcc13>3.0.co;2-m
Subject(s) - msh6 , microsatellite instability , biology , genetics , allele , gene , microsatellite , genome instability , mutation , coding region , dna mismatch repair , mutation rate , cancer research , dna , dna repair , dna damage
Two grades (high and low) of microsatellite instability (MSI) are known, depending on the number of mutated markers and the amount of allelic shifts. Forty‐two colorectal tumors, previously found to have high‐degree MSI at dinucleotidic repeat loci, were revisited with BAT26, a mononucleotide marker, and the number of shifted bases were counted. Seven tumors, all with local stages at diagnosis, had ≤6‐bp deletions and consistently displayed shorter shifts also with other intronic mononucleotide markers. Analysis of mononucleotide tracts in the coding regions of MSH3 , MSH6 , BAX , and TGFβRII in the groups with large (>6 bp) and short (≤6 bp) allelic shifts showed specific patterns of involvement for the individual genes: TGFβRII displayed a uniformly high rate of mutations, while MSH3 , MSH6 , and BAX were less frequently altered in tumors with short shifts. Our findings suggest that microsatellite instability arises gradually, evenly involving loci with similar features of length and repetition. However, target genes have a specific timing of mutation in this process: TGFβRII is involved in the early phases, while BAX and MSH6 are frequently associated with big size shifts and tumors with more advanced stages. Genes Chromosomes Cancer 27:424–429, 2000. © 2000 Wiley‐Liss, Inc.