Identification of new beta-catenin target genes using genome-wide analyses of chromatin structure

• Project/Area Number: 16K19075
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• 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): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 肝細胞癌 / ゲノム / エピゲノム / FAIRE / CTNNB1 / β-catenin / クロマチン構造 / 癌 / 遺伝子

Outline of Final Research Achievements

Itis known that not only genetic changes but also epigenetic alterations are important for the genesis and prognosis of cancer. In this project, we focused on beta-catenin (CTNNB1) mutations in hepatocellular carcinoma and revealed how these beta-catenin mutations affect the chromatin structure using integrated genome-wide analyses. Briefly we detected changes in chromatin structure, which were specific to the beta-catenin mutations. Finally we identified novel direct targets of beta-catenin, which might be candidates for therapeutic targets.

Research Products

• [Journal Article] CPT2 downregulation adapts HCC to lipid-rich environment and promotes carcinogenesis via acylcarnitine accumulation in obesity (2018)
  • Author(s): Fujiwara Naoto、Nakagawa Hayato、Enooku Kenichiro、Otsuka Motoyuki、Tateishi Keisuke、Koike Kazuhiko
  • Journal Title: Gut Volume: 67 Issue: 8 Pages: 1493-1504
  • DOI: 10.1136/gutjnl-2017-315193
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Contrast-enhanced intraoperative ultrasound in the resection of colorectal liver metastases with intrabiliary growth. (2018)
  • Author(s): Hiroyoshi J, Yamashita S, Tanaka M, Hayashi A, Ushiku T, Kaneko J, Akamatsu N, Arita J, Sakamoto Y, Hasegawa K.
  • Journal Title: Clin J Gastroenterol. Volume: Apr 9. Issue: 5 Pages: 348-353
  • DOI: 10.1007/s12328-018-0858-0
• [Journal Article] Safety and efficacy of venous reconstruction in liver resection using cryopreserved homologous veins. (2017)
  • Author(s): Yamamoto M, Akamatsu N, Hayashi A, Togashi J, Sakamoto Y, Tamura S, Hasegawa K, Fukayama M, Makuuchi M, Kokudo N.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: Sep;24(9) Issue: 9 Pages: 511-519
  • DOI: 10.1002/jhbp.488
• [Journal Article] Intrahepatic cholangiocarcinoma frequently shows loss of BAP1 and PBRM1 expression, and demonstrates specific clinicopathological and genetic characteristics with BAP1 loss. (2017)
  • Author(s): Misumi K*, Hayashi A* (*equal cotributions), Shibahara J, Arita J, Sakamoto Y, Hasegawa K, Kokudo N, Fukayama M.
  • Journal Title: Histopathology. Volume: Apr;70(5) Issue: 5 Pages: 766-774
  • DOI: 10.1111/his.13127
  • Peer Reviewed
• [Journal Article] Reversion of serum VZV-IgG antibody preceding disseminated visceral varicella zoster after hematopoietic stem cell transplantation. (2017)
  • Author(s): Arakawa S, Kage H, Chino H, Hinata M, Hayashi A, Toya T, Noguchi S, Ushiku T, Yamauchi Y, Kurokawa M, Fukayama M, Nagase T.
  • Journal Title: Ann Hematol. Volume: Mar;96(3) Issue: 3 Pages: 529-530
  • DOI: 10.1007/s00277-016-2876-7
  • Peer Reviewed
• [Journal Article] Mizuno H, Koya J, Fujioka Y, Ibaraki T, Nakamura F, Hayashi A, Shinozaki-Ushiku A, Akamatsu N, Hasegawa K, Kokudo N, Fukuyama M, Kurokawa M. (2017)
  • Author(s): Extranodal NK/T cell lymphoma in a living donor liver transplant recipient.
  • Journal Title: Ann Hematol. Volume: Mar 9. Issue: 6 Pages: 1051-1052
  • DOI: 10.1007/s00277-017-2969-y
  • Peer Reviewed
• [Journal Article] Non-occlusive mesenteric ischemia localized in the transverse colon: a case report. (2017)
  • Author(s): Murono K, Ishihara S, Kawai K, Kaneko M, Sasaki K, Yasuda K, Otani K, Nishikawa T, Tanaka T, Kiyomatsu T, Hata K, Nozawa H, Hayashi A, Ushiku T, Fukayama M, Watanabe T.
  • Journal Title: Surg Case Rep. Volume: Dec;3(1) Issue: 1 Pages: 23-23
  • DOI: 10.1186/s40792-017-0299-x
  • Peer Reviewed
• [Journal Article] Small colorectal cancers resembling submucosal tumor with massive submucosal invasion and lymph node metastasis: A report of two cases and review of the literature. (2017)
  • Author(s): Shinagawa T, Ishihara S, Nozawa H, Murono K, Nishikawa T, Otani K, Sasaki K, Yasuda K, Tanaka T, Kiyomatsu T, Hata K, Kawai K, Yamaguchi H, Hayashi A, Tanaka M, Ushiku T, Fukayama M, Watanabe T.
  • Journal Title: Clin Res Hepatol Gastroenterol. Volume: Mar;41(2) Issue: 2 Pages: e19-e23
  • DOI: 10.1016/j.clinre.2016.07.007
  • Peer Reviewed
• [Journal Article] PIK3CA and AKT1 mutations in hidradenoma papilliferum. (2017)
  • Author(s): Goto K, Maeda D, Kudo-Asabe Y, Hibiya T, Hayashi A, Fukayama M, Ohashi K, Goto A.
  • Journal Title: J Clin Pathol. Volume: May;70(5) Issue: 5 Pages: 424-427
  • DOI: 10.1136/jclinpath-2016-204003
  • Peer Reviewed
• [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: Aug;40(8) Issue: 8 Pages: 1021-30
  • DOI: 10.1097/pas.0000000000000670
  • Peer Reviewed
• [Journal Article] Immunohistochemistry Using Monoclonal Antibody MsMab-2 Is Useful to Detect IDH1 R132L in Intrahepatic Cholangiocarcinoma. (2016)
  • Author(s): Hayashi A, Misumi K, Shibahara J, Kokudo N, Kato Y and Fukayama M.
  • Journal Title: Pathology international Volume: 66 Issue: 10 Pages: 578-582
  • DOI: 10.1111/pin.12459
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Heart Failure Complicated by Alveolar Hemorrhage due to Vascular Collapse and Amyloid Deposits in Wild-Type Transthyretin Amyloidosis. (2016)
  • Author(s): Kido Y, Takahashi M, Fukuma N, Kawata T, Tanaka A, Hayashi A, Shibahara J, Daimon M, Morita H, Akazawa H, Komuro I.
  • Journal Title: Cardiology. Volume: 135(4) Pages: 216-220
  • Peer Reviewed
• [Journal Article] Primary hepatic schwannoma: A case report. (2016)
  • Author(s): Yamamoto M, Hasegawa K, Arita J, Maeno R, Akamatsu N, Kaneko J, Watadani T, Okura N, Hayashi A, Shibahara J, Sakamoto Y, Ohtomo K, Fukayama M, Kokudo N.
  • Journal Title: Int J Surg Case Rep. Volume: 29 Pages: 146-150
  • DOI: 10.1016/j.ijscr.2016.11.009
  • Peer Reviewed
• [Presentation] 次世代シーケンスによる肝細胞癌のクロマチンアクセシビリティ解析 (2016)
  • Author(s): 吉川修平、牧瀬尚大、林玲匡、藤田隆教、野村征太郎、永江玄太、緑川泰、深山正久、油谷浩幸
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] 肝がんにおけるエンハンサー領域のエピゲノム異常 (2016)
  • Author(s): 永江玄太、Renard-Guillet, Claire、辰野健二、山本尚吾、上田宏生、林玲匡、牧瀬尚大、緑川 泰、中川英刀、柴田龍弘、油谷 浩幸
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] 肝細胞がんの非癌部でのドライバー遺伝子変異 (2016)
  • Author(s): 辰野健二、山本尚吾、永江玄太、林玲匡、緑川泰、油谷浩幸
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] Alpha-Fetoprotein(AFP)産生胃癌のゲノム解析 (2016)
  • 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75回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] 肝内胆管癌における2つのサブタイプの臨床病理学的および遺伝学的特徴 (2016)
  • Author(s): 林玲匡、三角健人、柴原純二、有田 淳一、阪本良弘、長谷川潔、國土典弘、深山正久
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-05-12
• [Presentation] 肝細胞癌における腫瘍内リンパ球・形質細胞浸潤の組織学的アプローチ (2016)
  • Author(s): 林玲匡、柴原純二、三角健人、有田 淳一、阪本良弘、長谷川潔、國土典弘、深山正久
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-05-12
• [Presentation] 高感度ISH法による肝内胆管癌におけるアルブミンmRNA発現検討 (2016)
  • Author(s): 三角健人、柴原純二、林玲匡、國土 典弘、深山正久
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-05-12
• [Remarks] 東京大学医学部 人体病理学・病理診断学分野のウェブサイト 業績・年報
  • URL: http://pathol.umin.ac.jp/staff.shtml