Mutations of microsatellite instability target genes in sporadic basal cell carcinomas

Microsatellite instability (MSI) caused by a defective DNA mismatch repair (MMR) system is one of the phenotypes of genomic instability, accounting for the tumorigenesis of certain types of cancers conveying clinical and prognostic significance. Genes such as TGF-βRII, IGFIIR, hMSH3, and hMSH6 include coding mononucleotide repeats that are known targets for mutations in MSI-high tumors. The aim of our study was to investigate the prevalence of mutations in the above 4 MSI target genes in correlation with the MSI status of 75 basal cell carcinomas (BCCs), including aggressive-growth BCCs and cases with perineural invasion. TGF-βRII or hMSH3 frameshift mutations were identified in 5% of the BCCs, including two cases of aggressive-growth subtype, whereas there were no microsatellite alterations in the IGFIIR and hMSH6 genes. Mutations at the mononucleotide repeats within the hMSH3 and TGF-βRII genes occurred in certain BCCs, not always in association with MSI. It seems likely that microsatellite alterations may be important in the development of individual cases of BCCs despite the low frequency of MSI in our cohort.