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Altered expression of MUTYH and an increase in 8-hydroxydeoxyguanosine are early events in ulcerative colitis-associated carcinogenesis

Authors

  • Masaki Gushima,

    1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
    2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
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  • Minako Hirahashi,

    Corresponding author
    1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
    • Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
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  • Takayuki Matsumoto,

    1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
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  • Kouhei Fujita,

    1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
    2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
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  • Ritsuko Fujisawa,

    1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
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  • Kazuhiro Mizumoto,

    1. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
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  • Yusaku Nakabeppu,

    1. Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
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  • Mitsuo Iida,

    1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
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  • Takashi Yao,

    1. Department of Human Pathology, Juntendo University School of Medicine, Hongou 2-1-1, Bunkyou-ku, Tokyo 113-8421, Japan
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  • Masazumi Tsuneyoshi

    1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
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  • No conflicts of interest were declared.

Abstract

8-Hydroxy-guanine (8-OH-G) mismatches readily with adenine residues, leading to a G : C to T : A transversion mutation. The human mutY homologue (MUTYH) excises adenine misincorporated opposite 8-OH-G during replication and suppresses mutations caused by reactive oxygen species. We defined the expression of 8-hydroxydeoxyguanosine (8-OHdG) and MUTYH in ulcerative colitis (UC)-associated neoplasia by immunohistochemistry and compared this with expression in UC patients without neoplasia and patients unaffected by UC. We also performed mutation analyses for MUTYH and K-ras. 8-OHdG was expressed more intensely in the mucosa of UC-associated neoplasia and UC without neoplasm than in the mucosa unaffected by UC. Immunohistochemistry with two different types of MUTYH antibody showed that UC-associated neoplasia and UC without neoplasia exhibited strong cytoplasmic expression and attenuated nuclear expression of MUTYH when compared with patients unaffected by UC. No pathological MUTYH mutations were detected in any of the UC-associated neoplasia cases. However, K-ras mutation was detected in two cases, one of which showed G : C to T : A transversion mutation and attenuated nuclear staining of MUTYH. In conclusion, inflamed mucosa of UC is exposed to oxidative damage. An increase in cytoplasmic MUTYH, rather than its mutation, may contribute to the promotion of carcinogenesis in UC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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