Copy number analysis for stepwise hepatocarcinogenesis using early hepatocellular carcinoma

• Project/Area Number: 19591601
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Teikyo University
• Principal Investigator: MIDORIKAWA Yutaka Teikyo University, 医学部, 講師 (10292905)
• Co-Investigator(Kenkyū-buntansha): 石川 俊平 東京大学, 大学院・医学系研究科, 助教 (50418638)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 遺伝子 / 癌 / ゲノム / 病理学 / マイクロアレイ

Research Abstract

わが国における肝細胞癌の90%以上の症例は肝炎ウィルス罹患による慢性肝疾患を発生母地としており、前癌病変である再生結節や腺腫様過形成から早期肝癌へと移行する。本研究ではSNPアレイを用いたコピー数解析法により早期肝癌から進行肝癌へと進展する過程での染色体変化を明らかにし、また肝癌進展に寄与する癌抑制遺伝子CSMD1を同定し、同遺伝子のプロモーター領域におけるメチル化による不活化が重要であることを示した。

Research Products

• [Journal Article] Allelic imbalances and homozygous deletion on 8p23. 2 for stepwise progression of hepatocarcinogenesis (2009)
  • Author(s): Midorikawa Y, Yamamoto S, Tsuji S, Kamimura N, Ishikawa S, Igarashi H, Makuuchi M, Kokudo N, Sugimura H, Aburatani H
  • Journal Title: Hepatology 49 Pages: 513-22
• [Journal Article] Copy number estimation algorithms and fluorescence in situ hybridization to describe copy number alterations in human tumors (2009)
  • Author(s): Suzuki M, Nagura K, Igarashi H, Tao H, Midorikawa Y, Kitayama Y, Sugimura H
  • Journal Title: Pathol Int 59 Pages: 218-28
  • NAID: 10027379687
• [Journal Article] Allelic imbalances and homozygous deletion on 8p23.2for stepwise progression of hepatocarcinogenesis. (2009)
  • Author(s): Midorikawa Y
  • Journal Title: Hepatology 49 Pages: 513-522
  • Peer Reviewed
• [Journal Article] Copy number estimation algorithms and fluorescence insitu hybridization to describe copy number alterationsin human tumors. (2009)
  • Author(s): Suzuki M
  • Journal Title: Pathol Int. 59 Pages: 218-228
  • Peer Reviewed
• [Journal Article] A human homolog of Notum, over-expressed in hepatocellular carcinoma, is transcriptionally regulated by ss-catenin/TCF (2008)
  • Author(s): Torisu Y, Watanabe A, Nonaka A, Midorikawa Y, Makuuchi M, Shimamura T, Sugimura H, Niida A, Akiyama T, Iwanari H, Kodama T, Zeniya M, Aburatani H
  • Journal Title: Cancer Sci 99 Pages: 1139-16
• [Journal Article] Screening of liver-targeted drugs (2008)
  • Author(s): Midorikawa Y, Sugiyama Y, Aburatani H
  • Journal Title: Expert Opin Drug Discov 3 Pages: 643-54
• [Journal Article] Elevation of serum KL-6 mucin levels in patients with cholangiocarcinoma (2008)
  • Author(s): Xu H, Inagaki Y, Tang W, Guo Q, Wang F, Seyama Y, Midorikawa Y, Gai R, Kokudo N, Sugawara Y, Nakata M, Makuuchi M
  • Journal Title: Hepatogastroenterology 55 Pages: 2000-4
• [Journal Article] 非代償性肝硬変患者の栄養治療 (2008)
  • Author(s): 緑川蚕、村田宣夫、杉山保幸
  • Journal Title: 日門亢会誌 14(2) Pages: 164-166
  • NAID: 130004635736
• [Journal Article] A human homolog of Notum, over-expressed in hepatocellularcarcinoma, is transcriptionally regulated by 6-catenin/TCF. (2008)
  • Author(s): Torisu Y
  • Journal Title: Cacner Sci. 99 Pages: 1139-1146
  • Peer Reviewed
• [Journal Article] Screening of liver-targeted drugs. (2008)
  • Author(s): Midorikawa Y
  • Journal Title: Expert Opin Drug Discov. 3 Pages: 643-654
  • Peer Reviewed
• [Journal Article] Elevation of serum KL-6 mucin levels in patients withcholangiocarcinoma. (2008)
  • Author(s): Xu H
  • Journal Title: Hepatogastroenterol. 55 Pages: 2000-2004
  • Peer Reviewed
• [Journal Article] High-resolution mapping of copy number aberrations and identification of target genes in hepatocellular carcinoma (2007)
  • Author(s): Midorikawa Y, Tang W, Sugiyama Y
  • Journal Title: Bioscience Trends 1 Pages: 26-32
• [Journal Article] A case of cystic duct drainage into the left intrahepatic duct and the importance of Laparoscopic Fundus-First-Cholecystectomy for prevention of bile duct injury (2007)
  • Author(s): Yamakawa T, Tianhua Z, Midorikawa Y, Ishiyama J, Takahashi K, Sugiyama Y
  • Journal Title: J Laparoscopic Adv Surg Tech 17 Pages: 662-5
• [Journal Article] Inflammatory pseudotumor of the spleen : clinical impact in surgical treatment (2007)
  • Author(s): Takamoto K, Midorikawa Y, Minagawa M, Makuuchi M
  • Journal Title: Bioscience Trends 1 Pages: 113-6
• [Journal Article] Microarray-based analysis for hepatocellular carcinoma-from gene expression profiling to new challenges (2007)
  • Author(s): Midorikawa Y
  • Journal Title: World J Gastroenterol. 13 Pages: 1487-1492
  • Peer Reviewed
• [Journal Article] High-resolution mapping of copy number aberrations and identification of target genes in hepatocellular carcinoma (2007)
  • Author(s): Midorikawa Y
  • Journal Title: Bioscience Trends 1 Pages: 26-32
  • Peer Reviewed
• [Journal Article] KL-6 mucin is a useful immunohistochemical marker for cholangiocarcinoma (2007)
  • Author(s): Tang W
  • Journal Title: Oncol Rep 17 Pages: 737-742
  • Peer Reviewed
• [Journal Article] Inflammatory pseudotumor of the spleen: clinical impact in surgical treatment (2007)
  • Author(s): Takamoto K
  • Journal Title: Bioscience Trends 1 Pages: 113-116
  • Peer Reviewed
• [Journal Article] A case of cystic duct drainage into the left intrahepatic duct and the importance of Laparoscopic Fundus-First-Cholecystectomy for prevention of bile duct injury (2007)
  • Author(s): Yamakawa T
  • Journal Title: J Laparoscopic Adv Surg Tech 17 Pages: 662-665
  • Peer Reviewed
• [Presentation] 肝癌におけるゲノム・エピゲノム異常の統合的解析 (2008)
  • Author(s): 永江 玄太
  • Organizer: 第67回日本癌学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-28
• [Presentation] Amplification screening by FISH using tissue microarray and BAC probes (2008)
  • Author(s): 椙村 春彦
  • Organizer: 第67回日本癌学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-28
• [Presentation] SNPアレイを用いた決定木による肝癌進展に寄与する染色体領域の同定 (2008)
  • Author(s): 緑川 泰
  • Organizer: 第20回日本肝胆膵外科学会学術集会
  • Place of Presentation: 山形市
  • Year and Date: 2008-05-30
• [Presentation] Stepwise progression of allele imbalance in hepatocarcin ogenesis with special reference to nodule-in-nodule appearance using decision tree analysis. (2008)
  • Author(s): Midorikawa Y
  • Organizer: 99th, American Association for Cancer Research
  • Place of Presentation: San Diego
  • Year and Date: 2008-04-13
• [Presentation] Integrated analysis of genetic and epigenetic alterations in liver cancer. (2008)
  • Author(s): Nagae G
  • Organizer: 99th, American Association for Cancer Research
  • Place of Presentation: San Diego
  • Year and Date: 2008-04-13
• [Presentation] Glypican3は根治的肝切除後の肝癌再発予測マーカーとして有用である (2007)
  • Author(s): 渡邊 清高
  • Organizer: 第43回日本肝臓病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-18
• [Presentation] 肝癌治療後の血清Glypican3の陽性化は術後再発のマーカーとなりうる (2007)
  • Author(s): 渡邊 清高
  • Organizer: 第11回日本肝臓病学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-18
• [Presentation] Identification of chromosomal alterations associated with liver metastasis in colorectal carcinoma (2007)
  • Author(s): 山本 尚吾
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] 新規Wntターゲット遺伝子NOTUMの同定と肝臓癌における異常発現 (2007)
  • Author(s): 渡辺 亮
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] プロモーターアレイを用いた肝癌の網羅的メチル化解析 (2007)
  • Author(s): 永江 玄太
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Genome-wide approach for identification of allele imbalance region in hepatocarcinogenesis using single nucleotide polymorphism arrays. (2007)
  • Author(s): Midorikawa Y
  • Organizer: 98th, American Association for Cancer Research
  • Place of Presentation: Los Angeles
  • Year and Date: 2007-04-15
• [Presentation] A human homolog of Notum, overexpressed in hepatocellular carcinoma, is transcriptionally regulated by beta-catenin/TCF (2007)
  • Author(s): Watanabe A
  • Organizer: 98th, American Association for Cancer Research
  • Place of Presentation: Los Angeles
  • Year and Date: 2007-04-15
• [Presentation] Comprehensive DNA methylation analysis in human cancer using oligonucleotide tiling array (2007)
  • Author(s): Nagae G
  • Organizer: 98th, American Association for Cancer Research
  • Place of Presentation: Los Angeles
  • Year and Date: 2007-04-14
• [Presentation] Stepwise progression of allele imbalance in hepatocarcinogenesis with special reference to nodule-in-nodule appearance using decision tree analysis
  • Author(s): Yutaka Midorikawa, Shogo Yamamoto, Shingo Tsuji, Naoko Kamimura, Shumpei Ishikawa, Masatoshi Makuuchi, Hisaki Igarashi, Haruhiko Sugimura, Hiroyuki Aburatani
  • Organizer: 99th, American Association for Cancer Research
  • Place of Presentation: San Diego
• [Presentation] Integrated analysis of genetic and epigenetic alterations in liver cancer
  • Author(s): Genta Nagae, Atsushi kaneda, Shuichi Tsutsumi, Shumpei Ishikawa, Yutaka Midorikawa, Hiroyuki Aburatani
  • Organizer: 99th, American Association for Cancer Research
  • Place of Presentation: San Diego
• [Presentation] Prediction of efficacy of FOLFOX therapy for colorectal cancer patients using random forests analysis
  • Author(s): Yutaka Midorikawa, Yasuyuki Sugiyama, Shingo Tsuji, Koichi Yagi, Shogo Yamamoto, Kazuhiro Yoshida, Takao Takahashi, Hiroyuki Aburatani
  • Organizer: 100th, American Association for Cancer Research
  • Place of Presentation: Denver
• [Book] 肝癌のアレイ解析 (2008)
  • Author(s): 緑川泰、杉山保幸
  • Publisher: 遺伝子医学MOOK
• [Book] 遺伝子医学MOOK (2008)
  • Author(s): 緑川 泰
  • Publisher: 肝癌のアレイ解析