Intrachromosomal genomic instability in human sporadic colorectal cancer measured by genome-wide allelotyping and inter-(simple sequence repeat) PCR

We have used genome-wide allelotyping with 348 polymorphic autosomal marker s spaced, on average, 10 cM apart to quantitate the extent of intrachromoso mal instability in 59 human sporadic colorectal carcinomas. We have compare d instability measured by this method with that measured by inter-(simple s equence repeat) PCR and microsatellite instability assays. Instability quan titated by fractional allelic loss rates was found to be independent of tha t detected by microsatellite instability analyses but was weakly associated with that measured by inter-(simple sequence repeat) PCR. A set of seven l oci were identified that were most strongly associated with elevated rates of fractional allelic loss and/or inter-(simple sequence repeat) PCR instab ility; these seven loci were on chromosomes 3, 8, 11, 13, 14, 18, and 20. A lesser association was seen with two loci flanking p53 on chromosome 17. C oordinate loss patterns for these loci suggest that at least two separate s ets of cooperating loci exist for intrachromosomal genomic instability in h uman colorectal cancer.