Identification of target genes for esophageal cancers through integrative analysis of genomic alterations and oncogene addiction

• Project/Area Number: 20591564
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: IMOTO Issei Tokyo Medical and Dental University, 大学院・ヘルスバイオサイエンス研究部, 教授 (30258610)
• Co-Investigator(Kenkyū-buntansha): INAZAWA Johji 東京医科歯科大学, 難治疾患研究所, 教授 (30193551)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 食道癌 / アレイCGH / 遺伝子増幅 / DNAメチル化 / 癌遺伝子中毒 / アイレCGH / 癌抑制遺伝子中毒

Research Abstract

In order to identify target tumor-related genes for establishing molecular targeting therapy in patients with esophageal squamous-cell carcinoma, we integrated detailed information of genomic/epigenomic alterations in tumors, functional addiction of tumor cells to candidate target genes (oncogene addiction), and clinicopathological significance of altered expression status of those genes. Using this approach, we successfully identified a number of possible novel onocogene and tumor suppressor genes, which may be useful therapeutic as well as diagnostic targets for esophageal cancers.

Research Products

• [Journal Article] YAP is a candidate oncogene for esophageal squamous cell carcinoma. (2011)
  • Author(s): Muramatsu T, Imoto I, Matsui T, Kozaki K, Haruki S, Sudol M, Shimada Y, Tsuda H, Kawano T, Inazawa J.
  • Journal Title: Carcinogenesis 32 Pages: 389-398
  • Peer Reviewed
• [Journal Article] YAP is a candidate oncogene for esophageal squamous-cell carcinoma. (2011)
  • Author(s): Muramatsu T, Imoto I, et al.
  • Journal Title: Carcinogensis Volume: 32 Pages: 389-398
  • Peer Reviewed
• [Journal Article] Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous cell carcinoma. (2010)
  • Author(s): Haruki S, Imoto I, Kozaki K, Matsui T, Kawachi H, Komatsu S, Muramatsu T, Shimada Y, Kawano T, Inazawa J.
  • Journal Title: Carcinogenesis 31 Pages: 1027-1036
  • Peer Reviewed
• [Journal Article] miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. (2010)
  • Author(s): Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J.
  • Journal Title: Carcinogenesis 31 Pages: 766-776
  • Peer Reviewed
• [Journal Article] Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous-cell carcinoma. (2010)
  • Author(s): Haruki S, Imoto I, et al.
  • Journal Title: Carcinogensisr Volume: 31 Pages: 1027-1036
  • Peer Reviewed
• [Journal Article] miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. (2010)
  • Author(s): Furuta M, Imoto I, et al
  • Journal Title: Carcinogensis Volume: 31 Pages: 766-776
  • Peer Reviewed
• [Journal Article] Identification of PAK4 as a putative target gene for amplification within 19q13.12-q13.2 in oral squamous-cell carcinoma. (2009)
  • Author(s): Begum A, Imoto I, Kozaki K, Tsuda H, Suzuki E, Amagasa T, Inazawa J.
  • Journal Title: Cancer Sci 100 Pages: 1908-1916
  • Peer Reviewed
• [Journal Article] Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma. (2009)
  • Author(s): Komatsu S, Imoto I, Tsuda H, Kozaki KI, Muramatsu T, Shimada Y, Aiko S, Yoshizumi Y, Ichikawa D, Otsuji E, Inazawa J.
  • Journal Title: Carcinogenesis 30 Pages: 1139-1146
  • Peer Reviewed
• [Journal Article] Identification of PAK4 as a putative target gene for amplification within 19q13.12-q13.2 in oral squamous-cell carcinoma (2009)
  • Author(s): Begum A, Imoto I, et al.
  • Journal Title: Cancer Sci 100 Pages: 1908-1916
  • Peer Reviewed
• [Journal Article] Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous-cell carcinoma (2009)
  • Author(s): Komatsu S, Imoto I, et al.
  • Journal Title: Carcinogenesis 30 Pages: 1139-1146
  • Peer Reviewed
• [Journal Article] ITCH is a putative target for a novel 20q11.22 amplification detected in anaplastic thyroid carcinoma cells by array-based comparative genomic hybridization. (2008)
  • Author(s): Ishihara T, Tsuda H, Hotta A, Kozaki K, Yoshida A, Noh JY, Ito K, Imoto I, Inazawa J.
  • Journal Title: Cancer Sci 99 Pages: 1940-1949
  • Peer Reviewed
• [Journal Article] Frequent inactivation of a putative tumor suppressor, angiopoietin-like protein 2, in ovarian cancer. (2008)
  • Author(s): Kikuchi R, Tsuda H, Kozaki K, Kanai Y, Kasamatsu T, Sengoku K, Hirohashi S, Inazawa J, Imoto I.
  • Journal Title: Cancer Res 68 Pages: 5067-5075
  • Peer Reviewed
• [Journal Article] Identification of SMURF1 as a possible target for 7q21.3-22.1 amplification detected in a pancreatic cancer cell line by in-house array-based comparative genomic hybridization. (2008)
  • Author(s): Suzuki A, Shibata T, Shimada Y, Murakami Y, Horii A, Shiratori K, Hirohashi S, Inazawa J, Imoto I.
  • Journal Title: Cancer Sci 99 Pages: 986-994
  • Peer Reviewed
• [Journal Article] Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. (2008)
  • Author(s): Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J.
  • Journal Title: Cancer Res 68 Pages: 2094-2105
  • Peer Reviewed
• [Journal Article] Frequent inactivation of a putative tumor suppressor, angiopoietin-likeprotein 2, in ovarian cancer. (2008)
  • Author(s): Kikuchi R, et al.
  • Journal Title: Cancer Res 68 Pages: 5067-75
  • Peer Reviewed
• [Journal Article] Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. (2008)
  • Author(s): Kozaki K, et al.
  • Journal Title: Cancer Res 68 Pages: 2094-105
  • Peer Reviewed
• [Journal Article] Frequent silencing of a putative tumor suppressor gene melatonin receptor 1 A (MTNRlA)in oral squamous-cell carcinoma. (2008)
  • Author(s): Nakamura E, et al.
  • Journal Title: Cancer Sci 99 Pages: 1390-400
  • Peer Reviewed
• [Journal Article] Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous-cell carcinoma
  • Author(s): Haruki S, Imoto I, et al.
  • Journal Title: Carcinogenesis (in press)
  • Peer Reviewed
• [Presentation] 食道扁平上皮癌において高頻度に発現抑制を受ける新規癌抑制遺伝子候補Protocadherin 17(PCDH17) (2010)
  • Author(s): 井本逸勢、春木茂雄、小崎健一、松井毅、河内洋、小松周平、村松智輝、嶋田裕、河野辰幸、稲澤譲治
  • Organizer: 日本人類遺伝学会第55回大会
  • Place of Presentation: さいたま
  • Year and Date: 2010-10-29
• [Presentation] 食道扁平上皮癌で高頻度に発現消失する新規癌抑制遺伝子候補protocadherin 17 (2010)
  • Author(s): 井本逸勢、春木茂男、小崎健一、松井毅、河内洋、小松周平、村松智輝、嶋田裕、河野辰幸、稲澤譲治
  • 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] 食道扁平上皮癌で高頻度に発現消失する新規癌抑制遺伝子protocadherin 17 (2010)
  • Author(s): 井本逸勢, 他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-23
• [Presentation] がんの統合的ゲノム・エピゲノム解析 (2009)
  • Author(s): 井本逸勢、稲澤譲治
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] がんの統合的ゲノム・エピゲノム解析 (2009)
  • Author(s): 井本逸勢
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] ゲノムワイドな統合的DNAメチル化異常解析による肝癌抑制遺伝子候補探索 (2009)
  • Author(s): 井本逸勢、松村聡、小崎健一、有井滋樹、稲澤譲治
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-26
• [Presentation] ヒト癌におけるゲノム一次構造異常領域から同定された増幅標的癌遺伝子候補としてのdual specificity phosphatase (2008)
  • Author(s): 井本逸勢、稲澤譲治
  • Organizer: 第31回日本分子生物学会年会・第81回日本生科学会大会・合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] エピゲノム異常で発現抑制を受ける新規口腔、食道扁平上皮癌抑制遺伝子候補の同定 (2008)
  • Author(s): 井本逸勢、井上純、稲澤譲治
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] エピゲノム異常で発現抑制を受ける新規口腔、食道扁平上皮癌抑制遺伝子候補の同定 (2008)
  • Author(s): 井本逸勢
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知)
  • Year and Date: 2008-10-29
• [Presentation] ゲノム構造解析による食道扁平上皮癌の標的遺伝子探索 (2008)
  • Author(s): 井本逸勢、稲澤譲治
  • Organizer: 第17回日本アポトーシス研究会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-08-02
• [Remarks] ホームページ
• [Remarks] 徳島大学・大学院ヘルスバイオサイエンス研究部・人類遺伝学
  • URL: http://plaza.umin.ac.jp/awahg/
• [Remarks] 東京医科歯科大学・難治疾患研究所・分子細胞遺伝
  • URL: http://www.tmd.ac.jp/mri/cgen/framepage.htm
• [Remarks] 東京医科歯科大学・難治疾患研究所・分子細胞遺伝CGHデータベース
  • URL: http://www.cghtmd.jp/cghdatabase/index.html
• [Remarks]
  • URL: http://www.cghtmd.jp/CGHDatabase/index_j.jsp
• [Patent(Industrial Property Rights)] 癌の検出方法および抑制方法 (2010)
  • Inventor(s): 稲澤譲治・小崎健一・井本逸勢・古田繭子・有井滋樹
  • Industrial Property Rights Holder: 富士フィルム株式会社・国立大学法人東京医科歯科大学
  • Filing Date: 2010-03-03
• [Patent(Industrial Property Rights)] 食道癌の検出又は予後の予測のための方法及び食道癌抑制剤 (2010)
  • Inventor(s): 稲澤譲治・井本逸勢・春木茂男
  • Industrial Property Rights Holder: 富士フィルム株式会社・国立大学法人東京医科歯科大学
  • Filing Date: 2010-02-26
• [Patent(Industrial Property Rights)] 食道癌の検出方法及び抑制剤 (2009)
  • Inventor(s): 井上純・井本逸勢・稲澤譲治
  • Industrial Property Rights Holder: 国立大学法人東京医科歯科大学・富士フィルム株式会社
  • Filing Date: 2009-03-25