Microsatellite Instability in Saliva from Patients with Hereditary Non-polyposis Colon Cancer and Siblings Carrying Germline Mismatch Repair Gene Mutations

Abstract. Microsatellites are short tandem repeats of deoxyribonucleic acid (DNA) sequences which are distributed throughout the genome. Tumors in patients with Lynch syndrome tend to accumulate muta-tions in microsatellites at a much higher rate than other sequences in the genome resulting in microsatel-lite instability (MSI). This is due to germline mutations in mismatch repair (MMR) genes. Using small pool-polymerase chain reaction (SP-PCR), previous studies have shown that mutant alleles can be detected in microsatellites of DNA from peripheral blood lymphocytes (PBLs) of Lynch syndrome patients at fre-quencies that were low, but significantly higher than frequencies in PBLs of age-matched non-Lynch syn-drome controls. In the present study, SP-PCR detection of frequency of mutant MSI alleles (FMMA) was performed on PBLs and saliva samples from four sets of families. Each family set consisted of a mutation carrying affected proband (initial tumor bearer), a germline mutation-carrier sibling without tumors, and an age-matched normal control, either related (for 3 family sets) without mutation carrier status or unre-lated (for 1 family set) without mutation carrier status. FMMAs of saliva and PBL DNA were compared between each proband, sibling and control for each family set, and between family sets. In all five statisti-cally significant saliva comparisons identified between germline mutation carriers (FMMA: 0.080–0.261) and normal controls (FMMA: 0.003–0.087), the measured FMMAs were always higher in the carriers (p &lt