Association of the SUV39H1 histone methyltransferase with the DNA methyltransferase 1 at mRNA expression level in primary colorectal cancer

Authors

  • Mi Yeon Kang,

    1. Center for Genome Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea
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    • The first two authors contributed equally to this project.

  • Bo Bin Lee,

    1. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
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    • The first two authors contributed equally to this project.

  • Young-Ho Kim,

    1. Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Dong Kyoung Chang,

    1. Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Seo Kyu Park,

    1. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Ho-Kyung Chun,

    1. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Sang Yong Song,

    1. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Joobae Park,

    1. Center for Genome Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea
    2. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
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  • Duk-Hwan Kim

    Corresponding author
    1. Center for Genome Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea
    2. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
    • Center for Genome Research, Samsung Biomedical Research Institute, Rm B155, #50 Ilwon-dong, Kangnam-Ku, Seoul, Korea 135-710
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    • Fax: +02-3410-3649.


Abstract

This study was aimed at investigating the involvement of the SUV39H1 histone methyltransferase on the epigenetic change of euchromatic promoter in colorectal cancer. We retrospectively analyzed the mRNA levels of SUV39H1 and the promoter methylation of the p14ARF, p16INK4a and HLTF genes as well as the mRNA levels of DNA methyltransferase 1 (DNMT1) in fresh frozen tissues from 219 colorectal cancer patients. The mRNA levels of the SUV39H1 and DNMT1 were assessed via quantitative real-time PCR and the methylation profiles of the CpG islands were determined using methylation-specific PCR. The mRNA levels of SUV39H1 and DNMT1 were elevated in 25% and 42% of 219 colorectal cancers, respectively. The hypermethylation of the p14ARF, p16INK4a and HLTF genes occurred in 36%, 51% and 34% of the patients. The elevated mRNA levels of SUV39H1 were not associated with the hypermethylation of the 3 genes. However, the mRNA levels of DNMT1 were significantly different between patients with elevated mRNA levels of SUV39H1 and those without (1.62 ± 0.84, 0.91 ± 0.81, respectively; p = 0.007). Patients with elevated mRNA levels of SUV39H1 showed a higher prevalence of DNMT1 elevation than those without (61 vs. 35%, p = 0.0008). Patients with an elevated mRNA level of SUV39H1 had a 2.71 (95% CI = 1.09–4.48, p = 0.002) times greater risk of an elevated mRNA level of DNMT1, after controlling for age and gender. In conclusion, the present study suggests that SUV39H1 is significantly associated with DNMT1, but not with euchromatic promoter methylation in colorectal cancer. © 2007 Wiley-Liss, Inc.

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