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2017 Fiscal Year Final Research Report

Attempt to search for environmental and genetic factors that enhance microsatellite instability in mismatch repair deficient human cells

Research Project

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Project/Area Number 16K12605
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Risk sciences of radiation and chemicals
Research InstitutionFukuoka Dental College (2017)
Kyushu University (2016)

Principal Investigator

TSUZUKI Teruhisa  福岡歯科大学, 口腔歯学部, 客員教授 (40155429)

Co-Investigator(Kenkyū-buntansha) 中津 可道  九州大学, 医学研究院, 准教授 (00207820)
Co-Investigator(Renkei-kenkyūsha) ODA Shinya  九州がんセンター, 臨床研究センター, 室長 (40333372)
Project Period (FY) 2016-04-01 – 2018-03-31
Keywordsゲノム不安定性 / 大腸がん / ミスマッチ修復系
Outline of Final Research Achievements

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.

Free Research Field

分子遺伝学・放射線生物学

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Published: 2019-03-29  

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