Genome-wide analysis of DNA methylation in canine lymphoma

• Project/Area Number: 15K18789
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: YAMAZAKI JUMPEI 北海道大学, 獣医学研究科, 助教 (20732902)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: DNAメチル化 / エピジェネティクス / リンパ腫 / エピゲノム / 臨床 / 癌 / ゲノム

Outline of Final Research Achievements

Next-generation sequencing for 5 canine lymphoma cell lines was found to be quantitative so that 100,000 CpG sites could be analyzed. It also showed clearly difference in DNA methylation patterns between lymphoma cell lines and normal lymphocytes. We identified 1000-4000 hypermethylated and 3000-10000 hypomethylated CpG sites in each cell line. Genes known to be involved in tumor were found to be located close to the CpG sites hypermethylated in the cell lines.
The analysis for 24 spontaneous lymphoma cases indicated that DNA methylation pattern could be prognostic factor in canine lymphoma.

Research Products

• [Journal Article] A CpG island methylator phenotype in acute myeloid leukemia independent of IDH mutations and associated with a favorable outcome. (2017)
  • Author(s): Kelly AD, Kroeger H, Yamazaki J, Taby R, Neumann F, Yu S, Lee JT, Patel B, Li Y, He R, Liang S, Lu Y, Cesaroni M, Pierce SA, Kornblau SM, Bueso-Ramos CE, Ravandi F, Kantarjian HM, Jelinek J, Issa JP
  • Journal Title: Leukemia Volume: 印刷中 Issue: 10 Pages: 2011-2019
  • DOI: 10.1038/leu.2017.12
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Hypomethylation of TET2 target genes identifies a curable subset of acute myeloid leukemia. (2016)
  • Author(s): Yamazaki J, Taby R, Jelinek J, Raynal NJ, Cesaroni M, Pierce SA, Kornblau SM, Bueso-Ramos CE, Ravandi F, Kantarjian HM, Issa JP
  • Journal Title: J. Natl. Cancer Inst. Volume: 108 Issue: 2
  • DOI: 10.1093/jnci/djv323
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer. (2016)
  • Author(s): Tahara T, Shibata T, Okamoto Y, Yamazaki J, Kawamura T, Horiguchi N, Okubo M, Nakano N, Ishizuka T, Nagasaka M, Nakagawa Y, Ohmiya N
  • Journal Title: Oncotarget Volume: 7 Issue: 27 Pages: 42252-42260
  • DOI: 10.18632/oncotarget.9770
  • Peer Reviewed / Open Access
• [Journal Article] TET2 mutations affect non-CpG island DNA methylation at enhancers and transcription factor binding sites in chronic myelomonocytic leukemia. (2015)
  • Author(s): Yamazaki J, Jelinek J, Lu Y, Cesaroni M, Madzo J, Neumann F, He R, Taby R, Vasanthakumar A, Macrae T, Ostler KR, Kantarjian HM, Liang S, Estecio MR, Godley LA, Issa JP
  • Journal Title: Cancer Res. Volume: 75 Issue: 14 Pages: 2833-43
  • DOI: 10.1158/0008-5472.can-14-0739
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Methylome sequencing for fibrolamellar hepatocellular carcinoma depicts distinctive features. (2015)
  • Author(s): Malouf GG, Tahara T, Paradis V, Fabre M, Guettier C, Yamazaki J, Long H, Lu Y, Raynal NJ, Jelinek J, Mouawad R, Khayat D, Brugieres L, Raymond E, Issa JP
  • Journal Title: Epigenetics Volume: 10 Issue: 9 Pages: 872-81
  • DOI: 10.1080/15592294.2015.1076955
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 犬のリンパ腫における微小残存病変（MRD) (2015)
  • Author(s): 山崎淳平
  • Journal Title: Veterinary Oncology Volume: 5 Pages: 34-43
• [Presentation] イヌにおけるDNAメチル化のゲノムワイド解析法の樹立 (2017)
  • Author(s): 久本 真也, 山崎 淳平, 稲葉 睦
  • Organizer: 第13回 日本獣医内科学アカデミー（JCVIM）学術大会
  • Place of Presentation: パシフィコ横浜 横浜市
  • Year and Date: 2017-02-17
• [Presentation] Identification of TET2-specific differentially methylated CpG sites that define a curable subset of acute myeloid leukemia. (2015)
  • Author(s): Yamazaki J, Jelinek J, Cesaroni M, Madzo J, Taby R, Kantarjian HM, Godley LA and Issa JP
  • Organizer: 40th The Naito Conference
  • Place of Presentation: Chateraise Gateaux Kingdom Sapporo
  • Year and Date: 2015-09-15
  • Int'l Joint Research