Microsatellite instability in human cancer

Tumorigenesis has made tremendous progress through the recent identification of widespread alterations in tumor genomes, manifested as microsatellite instability. Several genes causing microsatellite instability have already been identified. This was considerably facilitated by the knowledge of homologous DNA mismatch repair genes in bacteria and yeast. Correspondingly, the human genes are also tightly linked to DNA mismatch repair. In addition, recent research showed that there must be other--yet unknown--genes that might also cause the genotype of microsatellite instability. Microsatellite instability has also provided a model for the proposed existence of mutator phenotypes by giving an explanation as to how the high number of mutations observed in malignant cells might accumulate. This review focuses on these genes and our current knowledge of their role in tumorigenesis and/or tumor progression. In addition, the occurrence of microsatellite instability in a large variety of tumors is reviewed in detail.