Research Project
Grant-in-Aid for Challenging Exploratory Research
Using the CRISPR/Cas9 genome editing technique, we established HeLa clones carrying MSH2 variations; G674R, G674D and G674A, those were reported in Lynch syndrome (LS) patients. These clones showed hyper resistance to MNU, with a characteristic feature of MMR-deficiency. And the mutation frequencies observed at the HPRT locus were uniformly elevated in these clones. Another hallmark of MMR deficiency is microsatellite instability (MSI) that is known to widely and drastically undergo length changes in MMR-defective tumors. However, microsatellite alterations in these clones were generally modest. Alterations in dinucleotide microsatellites were rare and, in all cases, within 6-bp, which corresponds to Type A instability that we have previously reported in Msh2-deficient mice. Mononucleotide repeats were stable in the clones. Accordingly, molecular defects, not yet discerned, should underlie genomic instability observed in MSI+ human tumors including ones developed in LS patients.
All 2017 2016
All Journal Article (4 results) (of which Int'l Joint Research: 1 results, Peer Reviewed: 4 results, Open Access: 4 results, Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 4 results, Invited: 5 results) Book (1 results)
Cancer Science
Volume: 108 Issue: 1 Pages: 108-115
10.1111/cas.13106
In Vivo
Volume: 30 Issue: 6 Pages: 769-776
10.21873/invivo.10993
Scientific Reports
Volume: 6 Issue: 1 Pages: 32399-32399
10.1038/srep32399
Free Radic. Biol. Med.
Volume: 99 Pages: 385-391
10.1016/j.freeradbiomed.2016.08.018
