Microsatellite instability in tumors as a model to study the process of microsatellite mutations

Abstract

We screened 42 sporadic gastric tumors and found that seven of them had significant microsatellite instability. These were then studied at 26 microsatellite loci, comprising di-, tri- and tetranucleotide repeats. The instability level of individual microsatellites in the tumors was found to be positively correlated with the population average heterozygosity and variance of repeat number of the microsatellite loci, as predicted by the stepwise mutation model. Moreover, as is known to occur in human populations, instability was strongly correlated with the number of repeats at each microsatellite locus and with the perfection of the reiterated sequence. These results demonstrate that microsatellite mutations in unstable tumors show similarities to germline mutations and suggest that their study may be useful in understanding the mechanisms that generate microsatellite variability in human populations. We used this model to test the claims that the microsatellite mutation process is biased towards increased size and heterozygosity with wide differences in allele sizes. These assertions were not confirmed.