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(American Journal of Pathology. 2001;158:1867-1870.)
© 2001 American Society for Investigative Pathology

Regular Articles

Stepwise Deletions of PolyA Sequences in Mismatch Repair-Deficient Colorectal Cancers

Corey Blake^*, Jen-Lan Tsao^*, Anna Wu and Darryl Shibata^*

From the Departments of Pathology^*
and Preventive Medicine,
University of Southern California School of Medicine, Los Angeles, California

PolyA simple repeat sequence deletions are common in tumors with microsatellite instability (MSI+). Such deletions occur one base at a time in DNA mismatch repair (MMR)-deficient yeast suggesting larger deletions in human MSI+ tumors represent multiple sequential stepwise losses. Sum total deletions in four polyA repeats were variable (between -17 to -45 bp) in 20 sporadic MSI+ colorectal cancers. Progressive but less extensive total deletions (maximum of -12 bp) occurred in similar polyA sequences in MMR-deficient mice (mlh1-/-) up to 478 days old. PolyA repeat lengths were relatively stable but already shortened in the MMR-deficient cell line HCT116. A transgene with 26 A’s transfected into HCT116 shortened an average of 3.8 bases pairs after 469 days in culture, less than average deletions of BAT25 (-5.3) or BAT26 (-9.0) in MSI+ cancers. These findings further suggest that extensive polyA deletions common in MSI+ tumors likely reflect multiple stepwise smaller deletions that accumulate more than hundreds of divisions after loss of MMR.

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