DETECTION OF A MUTATOR PHENOTYPE IN CANCER-CELLS BY INTER-ALU POLYMERASE CHAIN-REACTION

A mutator phenotype due to a DNA mismatch repair deficiency is usually detected by typing a number of microsatellite markers, Here, eight he reditary nonpolyposis colon cancer patients with microsatellite instab ility were investigated by inter-Alu PCR, known to amplify DNA segment s that may represent preferential targets of replication errors, Among 40-60 bands revealed in a single PCR experiment, more than 20% were f ound altered in tumoral DNA samples compared to matched normal samples from the same patient, Shifts and changes in signal intensity account ed for most of the alterations, whereas gains or losses of bands were rare, Certain bands were affected only in a single patient, whereas th e instabilities in others were common, These results suggest that some genomic regions are more susceptible than others to the expression of a mutator phenotype. Four such bands altered in at least five patient s were characterized further and shown to be unstable because of contr actions of the Alu poly(A) tails, Interestingly, none of the bands rep resenting loci shown previously to be polymorphic in the population di splayed instability in the tumoral samples, Inter-Alu PCR appears to b e a robust, cost-effective, and sensitive technique for revealing the mutator phenotype in cancer cells.