The instability within: problems in current analyses of microsatellite instability.
Microsatellite instability is regarded as one of the phenotypes of defective DNA mismatch repair and, consequently, as a marker of high risk for cancer. Despite numerous studies, the reported rates for positive microsatellite instability differ widely in each human malignancy. These discrepancies may relate to problems in the methods used. To establish a methodology for an accurate microsatellite instability analysis, technical requirements for a precise assay and biological conditions required for positive microsatellite instability were discussed. First, to describe microsatellite changes in detail, a sensitive detection system with linear detection characteristics and electrophoresis with standardised migration and minimised migration errors are considered to be necessary. Therefore, systems using fluorescent labelling and laser scanning are recommended. For reproducible polymerase chain reactions, it is essential to control the terminal deoxynucleotidyl transferase activity in Taq polymerase. Second, as a biological condition for positive microsatellite instability, feasible selection and combination of microsatellite markers, mutations in specific DNA mismatch repair genes and existence of monoclonal populations enriched sufficiently in a sample are essential. Finally, one possible diagnostic criterion for positive microsatellite instability is proposed, that is the existence of one of the patterns shown in the panel (see Fig. 6) at one or more loci in a set of more than five microsatellite markers.
Maehara
Y
Y
Cancer Center, Kyushu University Hospital, Kyushu University, Fukuoka 812-8582, Japan.
Oda
S
S
Sugimachi
K
K
D004260:DNA Repair / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
D005819:Genetic Markers