Stepwise deletions of polyA sequences in mismatch repair-deficient colorectal cancers

The American Journal of Pathology
C BlakeD Shibata

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.

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Citations

Mar 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jian LiLuigi Grasso
Mar 8, 2013·PLoS Genetics·Stéphanie ToméChristopher E Pearson
Jan 18, 2016·DNA Repair·Monika H M Schmidt, Christopher E Pearson
Feb 9, 2008·The Journal of Molecular Diagnostics : JMD·Vanessa DeschoolmeesterJan B Vermorken
Apr 12, 2002·The American Journal of Pathology·Hong WangLora Hedrick Ellenson
Apr 12, 2002·The American Journal of Pathology·Kyoung-Mee KimDarryl Shibata
Jun 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Gagan B PanigrahiChristopher E Pearson
Apr 28, 2010·Gastroenterology·C Richard Boland, Ajay Goel
Oct 22, 2005·Molecular Carcinogenesis·Jeffery W BacherRichard B Halberg
Jan 21, 2017·Nature Communications·Laura L ArthurSergej Djuranovic
Nov 26, 2003·Molecular Carcinogenesis·Omar KabbarahPaul J Goodfellow
Sep 16, 2006·Genes, Chromosomes & Cancer·Honor HugoRobert G Ramsay
Sep 21, 2012·The American Journal of Surgical Pathology·Yong H WenJinru Shia
Dec 17, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jinru ShiaDavid S Klimstra

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