Analysis of epigenomic abnormalities in Merkel cell carcinoma

• Project/Area Number: 17K15644
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Tottori University
• Principal Investigator: MATSUSHITA Michiko 鳥取大学, 医学部, 助教 (70642198)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: MCPyV / SWI/SNF複合体 / H3K27me3 / Notch / エピゲノム / メルケル細胞癌 / メルケル細胞ポリオーマウイルス / 遺伝子病理診断学

Outline of Final Research Achievements

Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor that occurs most often in elderly patients. Approximately 80% of MCCs harbor Merkel cell polyomavirus (MCPyV), thought to be a carcinogenic agent. In this study, modification of H3K27me3 was significantly lower in MCPyV-negative MCCs than in MCPyV-positive MCCs.

Academic Significance and Societal Importance of the Research Achievements

遺伝子発現やクロマチン状態は、ヒストン修飾を始めとしたエピジェネティクスな制御を受ける。H3K27me3の修飾状態がMCPyV陽性MCCとMCPyV陰性MCCで異なることからMCPyV陽性MCCとMCPyV陰性MCCでの遺伝子発現の差異の原因の一つである可能性が示唆され、治療法の開発へとつながる研究基盤となることが期待される。

Research Products

• [Journal Article] Decreased H3K27me3 Expression is Associated With Merkel Cell Polyomavirus-Negative Merkel Cell Carcinoma, Especially Combined With Cutaneous Squamous Cell Carcinoma (2019)
  • Author(s): Michiko Matsushita, Takeshi Iwasaki, Lusi Oka Wardhani, Satoshi Kuwamoto, Daisuke Nonaka, Keiko Nagata, Masako Kato , Yukisato Kitamura , Kazuhiko Hayashi
  • Journal Title: Anticancer Res. Volume: 39 Issue: 10 Pages: 5573-5579
  • DOI: 10.21873/anticanres.13751
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Expression of Notch 3 and Jagged 1 Is Associated With Merkel Cell Polyomavirus Status and Prognosis in Merkel Cell Carcinoma. (2019)
  • Author(s): Wardhani LO, Matsushita M, Kuwamoto S, Nonaka D, Nagata K, Kato M, Kitamura Y, Hayashi K
  • Journal Title: Anticancer Research Volume: 39 Issue: 1 Pages: 319-329
  • DOI: 10.21873/anticanres.13114
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The expression of Notch signaling pathway in Merkel cell carcinoma. (2019)
  • Author(s): Matsushita M, Lusi Oka Wardhani, Iwasaki T, Kuwamoto S, Nonaka D, Nagata K, Kato M, Kitamura Y, Hayashi K
  • Organizer: 31st European Congress of Pathology
  • Int'l Joint Research
• [Presentation] The histone modification H3K27me3 is reduced in MCPyV-negative Merkel cell carcinomas. (2018)
  • Author(s): Matsushita M, Iwasaki T, Kuwamoto S, Lusi Oka Wardhani, Nonaka D, Nagata K, Kato M, Kitamura Y, Hayashi K.
  • Organizer: 30th European Congress of Pathology
  • Int'l Joint Research
• [Presentation] メルケル細胞ポリオーマウイルス陰性のメルケル細胞癌では、ヒストンH3K27me3修飾が低下する (2018)
  • Author(s): 松下倫子、岩崎健、桑本聡史、野中大輔、長田佳子、加藤雅子、北村幸郷、林一彦
  • Organizer: 第107回日本病理学会総会
• [Presentation] Altered expression of SWI/SNF complex and its significance in Merkel cell carcinoma. (2017)
  • Author(s): Matsushita M, et al.
  • Organizer: 29th European Congress of Pathology
  • Int'l Joint Research