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Detection of a Mutator Phenotype in Cancer Cells by Inter-Alu Polymerase Chain Reaction¹

Service d'Hématologie-Oncologie, Centre de Cancérologie Charles Bruneau, Centre de Recherche de l'Hôpital Sainte-Justine [M. K., C. R., D. L., D. S.] and Département de Pédiatrie, Université de Montréal [D. L., D. S.], Montréal, Québec, Canada H3T 1C5

A mutator phenotype due to a DNA mismatch repair deficiency is usually detected by typing a number of microsatellite markers. Here, eight hereditary nonpolyposis colon cancer patients with microsatellite instability were investigated by inter-Alu PCR, known to amplify DNA segments that may represent preferential targets of replication errors. Among 40–60 hands revealed in a single PCR experiment, more than 20% were found altered in tumoral DNA samples compared to matched normal samples from the same patient. Shifts and changes in signal intensity accounted for most of the alterations, whereas gains or losses of bands were rare. Certain bands were affected only in a single patient, whereas the 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 patients were characterized further and shown to be unstable because of contractions of the Alu poly(A) tails. Interestingly, none of the bands representing loci shown previously to be polymorphic in the population displayed instability in the tumoral samples. Inter-Alu PCR appears to be a robust, cost-effective, and sensitive technique for revealing the mutator phenotype in cancer cells.

¹ This study was supported by the Fondation de l'Hôpital Sainte-Justine and the Fondation Charles Bruneau. D. S. is a scholar of the Fonds de la Recherche en Santé du Québec.

² To whom requests for reprints should be addressed, at the Division of Hemato-Oncology, Centre de Cancérologie Charles Bruneau, Hôpital Sainte-Justine, 3175 Côte Sainte-Catherine, Montréal, Québec, Canada H3T 1C5. Phone: (514) 345-4931, ext. 6142; Fax: (514) 345-4731; E-mail: sinnettd@ere.umontreal.ca.

Received 4/ 5/96. Accepted 5/ 7/96.

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