Microsatellite instability in cancer: What problems remain unanswered?

Analyses of microsatellite instability have been prevalent, particularly in the field of oncology. However, the literature on this subject is diverse. The discrepancies may derive from methodological problems in the conventional techniques used for analysis. Problems include low quantitativity in the detection systems, inaccurate migration in electrophoresis, and Taq polymerase-mediated modifications of polymerase chain reaction products. Indeed, use of a new fluorescent technique where these problems have been overcome has elucidated various intriguing and previously unrecognized aspects of microsatellite instability in human cancers. Patterns of microsatellite changes observed in various human cancers can be classified into 2 subtypes, those showing relatively small changes within 6 base pairs (type A) and those exhibiting drastic changes over 8 base pairs (type B). Although type A microsatellite instability has been connected to defective mismatch repair phenotype, the relationship between type B microsatellite instability and defective mismatch repair phenotype remains unclear. Nevertheless, as symbolized in cases of hereditary nonpolyposis colorectal cancer, connections between type B microsatellite instability and familial predisposition have been suggested in some cancers. The molecular background of type B microsatellite changes warrants particular attention.