PMID:11337385

Citation	Blake, C, Tsao, JL, Wu, A and Shibata, D (2001) Stepwise deletions of polyA sequences in mismatch repair-deficient colorectal cancers. Am. J. Pathol. 158:1867-70
Abstract	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.
Links	PubMed PMC1891934 Online version:10.1016/S0002-9440(10)64143-0
Keywords	Adaptor Proteins, Signal Transducing; Animals; Base Pair Mismatch/genetics; Carrier Proteins; Colorectal Neoplasms/genetics; Colorectal Neoplasms/metabolism; Colorectal Neoplasms/pathology; DNA/chemistry; DNA/genetics; DNA Mutational Analysis; DNA Repair; HT29 Cells; Humans; Intestines/metabolism; Mice; Mice, Knockout; Microsatellite Repeats/genetics; Mutation; Neoplasm Proteins/deficiency; Neoplasm Proteins/genetics; Nuclear Proteins; Poly A/genetics; Sequence Deletion; Tumor Cells, Cultured
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