Comprehensive Analysis of Chromatin Structure in Hepatocellular Carcinoma Based on Somatic Mutation

• Project/Area Number: 26893045
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Human pathology
• Research Institution: The University of Tokyo
• Principal Investigator: HAYASHI Akimasa 東京大学, 医学部附属病院, 助教 (40735396)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 肝細胞癌 / FAIRE / エピゲノム / ゲノム / クロマチン構造 / 網羅的解析 / クロマチン / ARID

Outline of Final Research Achievements

In genesis and progression of tumor, not only genetic changes (gene mutations) but also alteration of systems that regulate genes are required. In this research, we focused on chromatin structure composed of DNA and proteins as one of the regulation systems of genes, and tried to identify genome wide chromatin structure changes through genesis and progression of cancer. We identified the genome wide chromatin structure using frozen surgical specimens of hepatocellular carcinoma with the FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) method and a next generation sequencer, and compared the chromatin structure between hepatocellular carcinoma and background liver. By examining the chromatin structure changes based on the somatic mutations of oncogenes, we identified the regions of chromatin alteration specific to CTNNB1 mutation.

Research Products

• [Journal Article] Distinct clinicopathologic and genetic features of 2 histologic subtypes of intrahepatic cholangiocarcinoma. (2016)
  • Author(s): Hayashi A, Misumi K, Shibahara J, Arita J, Sakamoto Y, Hasegawa K, Kokudo N, Fukayama M.
  • Journal Title: Am J Surg Pathol. Volume: in press
  • Peer Reviewed
• [Journal Article] Clinicopathologic Characteristics of Hepatocellular Carcinoma With Reactive Ductule-like Components, a Subset of Liver Cancer Currently Classified as Combined Hepatocellular-Cholangiocarcinoma With Stem-Cell Features, Typical Subtype. (2016)
  • Author(s): Shibahara J, Hayashi A, Misumi K, Sakamoto Y, Arita J, Hasegawa K, Kokudo N, Fukayama M.
  • Journal Title: Am J Surg Pathol. Volume: 40(5) Issue: 5 Pages: 608-616
  • DOI: 10.1097/pas.0000000000000579
  • Peer Reviewed
• [Journal Article] β-catenin alteration is rare in hepatocellular carcinoma with steatohepatitic features: immunohistochemical and mutational study. (2015)
  • Author(s): Ando S, Shibahara J, Hayashi A, Fukayama M.
  • Journal Title: Virchows Archiv Volume: 467(5) Issue: 5 Pages: 535-42
  • DOI: 10.1007/s00428-015-1836-2
  • Peer Reviewed
• [Journal Article] Altered expression of AT-rich interactive domain 1A in hepatocellular carcinoma (2015)
  • Author(s): Hayashi A, Abe H, Kunita A, Sakamoto Y, Hasegawa K, Shibahara J, Kokudo N, Fukayama M
  • Journal Title: International Journal of Clinical and Experimental Pathology Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. (2014)
  • Author(s): Totoki Y, Tatsuno K, Covington KR, Ueda H, Creighton CJ, Kato M, Tsuji S, Donehower LA, Slagle BL, Nakamura H, Yamamoto S, Shinbrot E, Hama N, Lehmkuhl M, Hosoda F, Arai Y, Walker K, Dahdouli M, Gotoh K, Nagae G, Gingras MC, Muzny DM, …, Takayama T, Fukayama M, Gibbs RA, Wheeler DA, Aburatani H, Shibata T
  • Journal Title: Nat Genet. Volume: 46 Issue: 12 Pages: 1267-73
  • DOI: 10.1038/ng.3126
  • Peer Reviewed
• [Presentation] Distinct Clinicopathologic and Genetic Features of Two Histologic Subsets of Intrahepatic Cholangiocarcinoma (2016)
  • Author(s): Hayashi A, Misumi K, Shibahara J, Arita J, Sakamoto Y, Hasegawa K, Kokudo N, Fukayama M
  • Organizer: The 105th Annual Meeting of the United States and Canadian Academy of Pathology
  • Place of Presentation: Seattle, WA, USA
  • Year and Date: 2016-03-12
  • Int'l Joint Research
• [Presentation] Lymphocyte Infiltration is a New Promising Prognostic Factor in Hepatocellular Carcinoma (2016)
  • Author(s): Hayashi A, Shibahara J, Misumi K, Arita J, Sakamoto Y, Hasegawa K, Kokudo N, Fukayama M
  • Organizer: The 105th Annual Meeting of the United States and Canadian Academy of Pathology
  • Place of Presentation: Seattle, WA, USA
  • Year and Date: 2016-03-12
  • Int'l Joint Research
• [Presentation] 次世代シーケンスによる肝細胞癌のクロマチン構造解析 (2015)
  • Author(s): 牧瀬 尚大, 林 玲匡, 藤田 貴教, 永江 玄太, 緑川 泰, 深山 正久, 油谷 浩幸
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場，愛知県名古屋市
  • Year and Date: 2015-10-08
• [Presentation] Multi lesion analysis of alpha fetoprotein producing gastric cancer (2015)
  • Author(s): 田頭 周, 谷内田 真一, 垣内 美和子, 六反 啓文, 林 玲匡, 辰野 健二, 山本 尚吾, 永江 玄太, 阿部 浩幸, 石川 俊平, 柴田 龍弘, 深山 正久, 油谷 浩幸
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場，愛知県名古屋市
  • Year and Date: 2015-10-08
• [Presentation] 肝細胞癌背景肝組織におけるH3K27ac修飾レベルの臨床病理学的検討. (2015)
  • Author(s): 林玲匡, 柴原純二, 山内直子, 木村宏, 阪本良弘, 石川俊平, 國土典宏, 油谷浩幸,深山正久.
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場，愛知県名古屋市
  • Year and Date: 2015-04-30
• [Remarks] 東京大学 病理学教室 2015年度 業績
  • URL: http://pathol.umin.ac.jp/activity/gyoseki2015_1.pdf