| First Author | Blake C | Year | 2001 |
| Journal | Am J Pathol | Volume | 158 |
| Issue | 5 | Pages | 1867-70 |
| PubMed ID | 11337385 | Mgi Jnum | J:69102 |
| Mgi Id | MGI:1934053 | Doi | 10.1016/S0002-9440(10)64143-0 |
| Citation | Blake C, et al. (2001) Stepwise deletions of polyA sequences in mismatch repair-deficient colorectal cancers. Am J Pathol 158(5):1867-70 |
| abstractText | 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. |
