Analysis of epigenetic aberration in plasma cell dyscrasia

• Project/Area Number: 22790917
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Sapporo Medical University
• Principal Investigator: YASUI Hiroshi 札幌医科大学, 道民医療推進学講座, 助教 (40448593)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 血液内科学 / 難治性形質細胞疾患 / 多発性骨髄腫 / DNAメチル化 / 脱メチル化剤 / 抗癌剤感受性 / ゲノムワイド / 染色体異常 / 次世代シーケンサー / デキサメサゾン感受性

Research Abstract

We analyzed gene expression profile in MM cells treated with or without demethylating agent to screen for the tumor related genes silenced by DNA methylation. We next examined the effect of DNA hypomethylation in retrotransposon for chromosomal aberration. Patients in MM with chromosomal deletion showed significant lower LINE-1 methylation levels than patients without deletion suggesting that LINE-1 hypomethylation are associated with chromosomal instability. Our ongoing study is to decipher the methylome in MM cells using high-throughput next-generation sequencer ; and assess the association between the methylome status and the genome status.

Research Products

• [Journal Article] In vitro and in vivo antitumor effects of recombinant bispecific antibodies based on humanized anti-EGFR antibody (2011)
  • Author(s): Watanabe Y, Yasui H, et al
  • Journal Title: Oncol Rep Volume: 26(4) Pages: 949-55
  • DOI: 10.3892/or.2011.1382
  • Peer Reviewed
• [Journal Article] Interferon-α/β and anti-fibroblast growth factor receptor 1 monoclonal antibody suppress hepatic cancer cells in vitro and in vivo (2011)
  • Author(s): Sasaki S., et al
  • Journal Title: PLoS One Volume: 6 Issue: 5 Pages: e19618-e19618
  • DOI: 10.1371/journal.pone.0019618
  • Peer Reviewed
• [Journal Article] Epigenetic biomarkers for prediction of sensitivity to chemotherapeutic drugs in multiple myeloma (2011)
  • Author(s): Hiroshi Yasui
  • Journal Title: Tumor Research Volume: 45 Pages: 21-30
• [Journal Article] Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome (2010)
  • Author(s): Miyake N, Yasui H, et al
  • Journal Title: Hum Mutat Volume: 31(8) Issue: 8 Pages: 966-74
  • DOI: 10.1002/humu.21300
  • Peer Reviewed
• [Journal Article] PI3K/p110δis a novel therapeutic target in multiple myeloma (2010)
  • Author(s): Ikeda H, Yasui H, et al
  • Journal Title: Blood Volume: 116(9) Issue: 9 Pages: 1460-8
  • DOI: 10.1182/blood-2009-06-222943
  • Peer Reviewed
• [Journal Article] PI3K/p110δ is a novel therapeutic target in multiple myeloma. (2010)
  • Author(s): Hiroshi Ikeda
  • Journal Title: Blood Volume: 116 Pages: 1460-1468
  • Peer Reviewed
• [Journal Article] Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome (2010)
  • Author(s): Noriko Miyake
  • Journal Title: Human Mutation Volume: 31 Pages: 966-974
  • Peer Reviewed
• [Presentation] Epigenetic changes in repetitive elements are closely associated with genetic and clinical features in multiple myeloma (2011)
  • Author(s): Nojima M, Yasui H, et al
  • Organizer: The 39th Congress of the ISOBM
  • Place of Presentation: Firenze, Italy
  • Year and Date: 2011-10-17
• [Presentation] 次世代シーケンサーを用いた多発性骨髄腫におけるメチローム解析の試み (2011)
  • Author(s): 安井寛
  • Organizer: 73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-16
• [Presentation] 次世代シーケンサーを用いた多発性骨髄腫におけるメチローム解析の試み (2011)
  • Author(s): 安井寛, ら
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-16
• [Presentation] CD138抗体治療は骨髄微小環境下にいる骨髄腫細胞に対して細胞障害性を持つ (2011)
  • Author(s): 池田博, 安井寛ら
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] 多発性骨髄腫におけるDNAメチロームと染色体異常:メチル化DNA結合蛋白を利用した次世代シーケンシングによる検討 (2011)
  • Author(s): 野島正寛, 安井寛
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 多発性骨髄腫におけるDNA繰り返し配列の低メチル化と染色体異常の関連 (2011)
  • Author(s): 青木由佳, 安井寛
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] エピゲノム解析による造血器腫瘍の新たな分子標的の同定 (2011)
  • Author(s): 野島正寛, 安井寛
  • Organizer: 20回日本癌病態治療研究会年会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-17
• [Presentation] エピゲノム解析による造血器腫瘍の新たな分子標的の同定 (2011)
  • Author(s): 野島正寛, ら
  • Organizer: 第20回日本癌病態治療研究会年会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-17
• [Presentation] 多発性骨髄腫における次世代シーケンサーを利用したメチローム解析 (2011)
  • Author(s): 野島正寛, 安井寛
  • Organizer: 第5回日本エピジェネティックス研究会年会
  • Place of Presentation: 熊本
  • Year and Date: 2011-05-19
• [Presentation] Methylome analysis by the combination of methylated DNA enrichment and next-generation sequencing in multiple myeloma (2011)
  • Author(s): Nojima M, Yasui H, et al
  • Organizer: AACR 102nd Annual Meeting 2011
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2011-04-04
• [Presentation] 多発性骨髄腫におけるDNAメチル化遺伝子の網羅的スクリーニングおよびRASD1遺伝子メチル化のデキサメサゾン感受性への関与 (2010)
  • Author(s): 青木由佳, 安井寛
  • Organizer: 第35回日本骨髄腫研究会総会
  • Place of Presentation: 富山
  • Year and Date: 2010-11-20
• [Presentation] エピゲノム解析による造血器腫瘍の新たな分子標的の同定 (2010)
  • Author(s): 豊田実, 安井寛
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-26
• [Presentation] 未分化型胃癌におけるDNAメチル化異常の解明 (2010)
  • Author(s): 高丸博之, 安井寛
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] PI3K/p110δ阻害剤は多発性骨髄腫細胞に対して細胞障害性を有する (2010)
  • Author(s): 池田博, 安井寛
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] 多発性骨髄腫におけるDNAメチル化の網羅的解析と治療抵抗性予測への応用 (2010)
  • Author(s): 安井寛
  • Organizer: 第61回日本電気泳動学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-18
• [Book] II-3.発症機構とエピジェティックス異常6)多発性骨髄腫.造血器腫瘍とエピジェティクス-治療への応用と新たな展開- (2012)
  • Author(s): 安井寛, 石田禎夫
  • Publisher: 医薬ジャーナル社(in press)
• [Book] 造血器腫瘍とエピジェティクス-治療への応用と新たな展開- (2012)
  • Author(s): 安井寛、石田禎夫
  • Publisher: 医薬ジャーナル社(印刷中)
• [Remarks]
  • URL: http://jglobal.jst.go.jp/detail.php?JGLOBAL_ID=200901022350771168&t=1&d=1&q=%28205%29%3D1000307656