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

We screened 42 sporadic gastric tumors and found that seven of them had sig nificant microsatellite instability. These were then studied at 26 microsat ellite loci, comprising di-, tri- and tetranucleotide repeats. The instabil ity level of individual microsatellites in the tumors was found to be posit ively correlated with the population average heterozygosity and variance of repeat number of the microsatellite loci, as predicted by the stepwise mut ation model. Moreover, as is known to occur in human populations, instabili ty was strongly correlated with the number of repeats at each microsatellit e locus and with the perfection of the reiterated sequence. These results d emonstrate that microsatellite mutations in unstable tumors show similariti es to germline mutations and suggest that their study may be useful in unde rstanding 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 w ide differences in allele sizes. These assertions were not confirmed.