Genome-wide DNA methylation analysis in canine gastrointestinal lymphoma

  • OHTA Hiroshi
    Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan
  • YAMAZAKI Jumpei
    Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan
  • JELINEK Jaroslav
    Coriell Institute for Medical Research, 403 Haddon Ave, Camden, NJ 08103, USA
  • ISHIZAKI Teita
    Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan North Lab, Hokkaido, Hondori 2-chome, Kita 8-35, Shiroishi-ku, Sapporo, Hokkaido 003-0027, Japan
  • KAGAWA Yumiko
    North Lab, Hokkaido, Hondori 2-chome, Kita 8-35, Shiroishi-ku, Sapporo, Hokkaido 003-0027, Japan
  • YOKOYAMA Nozomu
    Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan
  • NAGATA Noriyuki
    Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan
  • SASAKI Noboru
    Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan
  • TAKIGUCHI Mitsuyoshi
    Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan

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<p>DNA methylation is the covalent modification of methyl groups to DNA mostly at CpG dinucleotides and one of the most studied epigenetic mechanisms that leads to gene expression variability without affecting the DNA sequence. Genome-wide analysis of DNA methylation identified the signatures that could define subtypes of human lymphoma patients. The objective of this study was to conduct the genome-wide analysis of DNA methylation in dogs with gastrointestinal lymphoma (GIL). Genomic DNA was extracted from endoscopic biopsies from 10 dogs with GIL. We performed Digital Restriction Enzyme Assay of DNA Methylation (DREAM) for genome-wide DNA methylation analysis that could provide highly quantitative information on DNA methylation levels of CpG sites across the dog genome. We successfully obtained data of quantitative DNA methylation level for 148,601–162,364 CpG sites per GIL sample. Next, we analyzed 83,132 CpG sites to dissect the differences in DNA methylation between GIL and normal peripheral blood mononuclear cells (PBMCs). We found 383–3,054 CpG sites that were hypermethylated in GIL cases compared to PBMCs. Interestingly, 773 CpG sites including promoter regions of 61 genes were identified to be commonly hypermethylated in more than half of the cases, suggesting conserved DNA methylation patterns that are abnormal in GIL. This study revealed that there was a large number of hypermethylated sites that are common in most of canine GIL. These abnormal DNA methylation could be involved in tumorigenesis of the canine GIL.</p>

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