Identification of novel tyrosine kinase fusion genes using a unique system based on morphology

• Project/Area Number: 22680063
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Tumor diagnosis
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: TAKEUCHI Kengo 公益財団法人がん研究会, がん研究所病理部, 主任研究員 (40323612)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000); Fiscal Year 2012: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000); Fiscal Year 2011: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000); Fiscal Year 2010: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: がん / チロシンキナーゼ / 融合遺伝子 / IRF4 / ALK / ROS1 / RET / SQSTM1-ALK / PPFIBP1-ALK

Research Abstract

We identified PPFIBP1-ALK in inflammatory myofibroblastic tumor and TPM3-ALK and EML4-ALK in renal cell carcinoma. In lymphoma, we found SQSTM1-ALK. KLC1-ALK was identified from a formalin-fixed paraffin-embedded (FFPE) tissue by RACE optimized for FFPE. We established a unique system for identification of fusion genes based on histopathological methods, and identified 4 ROS1 and 2 RET novel fusion genes. We also proposed a new entity of low-grade B-cell lymphoma, which was characterized by IRF4 rearrangement

Research Products

• [Journal Article] Epithelioid inflammatory myofibroblastic sarcoma arising in the pleural cavity (2013)
  • Author(s): Kozu Y, et al.
  • Journal Title: General Thoracic Cardiovascular Surgery Volume: 61 Issue: 3 Pages: 191-194
  • DOI: 10.1007/s11748-013-0204-x
  • Peer Reviewed
• [Journal Article] A low-grade B-cell lymphoma with prolymphocytic/paraimmunoblastic proliferation and IRF4 rearrangement (2013)
  • Author(s): Takeuchi K, et al
  • Journal Title: Haematologica Volume: 98 Issue: 3 Pages: e32-e35
  • DOI: 10.3324/haematol.2012.076851
  • Peer Reviewed
• [Journal Article] Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer oncoand suppressor gene changes (2013)
  • Author(s): Ninomiya H, et al.
  • Journal Title: BMC Cancer Volume: 13 Pages: 8-8
  • Peer Reviewed
• [Journal Article] Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco- and suppressor gene changes. (2013)
  • Author(s): Ninomiya H, et al. 13人中4番目
  • Journal Title: BMC Cancer Volume: 13 Issue: 1 Pages: 8-8
  • DOI: 10.1186/1471-2407-13-8
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): Soda M, Isobe K, Inoue A, Maemondo M,Oizumi S, Fujita Y, Gemma A, Yamashita Y,Ueno T, Takeuchi K, Choi YL, Miyazawa H,Tanaka T, Hagiwara K, Mano H
  • Journal Title: Clin Cancer Res Volume: 18 Issue: 20 Pages: 5682-5689
  • DOI: 10.1158/1078-0432.ccr-11-2947
  • Peer Reviewed
• [Journal Article] KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only (2012)
  • Author(s): Togashi Y, et al.
  • Journal Title: PLoS One Volume: 7 Issue: 2 Pages: 31323-31323
  • DOI: 10.1371/journal.pone.0031323
  • Peer Reviewed
• [Journal Article] RET, ROS1, and ALK fusions in lung cancer (2012)
  • Author(s): Takeuchi K, et al
  • Journal Title: Nature Medicine Volume: (In press) Issue: 3 Pages: 378-381
  • DOI: 10.1038/nm.2658
  • Peer Reviewed
• [Journal Article] Small non-mucinous bronchioloalveolar carcinoma with anaplastic lymphoma kinase immunoreactivity: A novel ALK fusion gene? (2012)
  • Author(s): Yamamoto M, et al.
  • Journal Title: Cancer Science Volume: 103 Issue: 2 Pages: 390-392
  • DOI: 10.1111/j.1349-7006.2011.02136.x
  • Peer Reviewed
• [Journal Article] Identification of ALK fusions in renal cancer : Large-scale immunohistochemical screening by intercalated antibody-enhanced polymer method (2012)
  • Author(s): Sugawara S, et al.
  • Journal Title: BJU int. Volume: (In press)(未定) Issue: 18 Pages: 4427-4436
  • DOI: 10.1002/cncr.27391
  • Peer Reviewed
• [Journal Article] ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity (2012)
  • Author(s): Kimura H, et al.
  • Journal Title: Lung Cancer Volume: 75 Pages: 66-72
  • Peer Reviewed
• [Journal Article] Favorable response to crizotinib in three patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion-type oncogene-positive non-small cell lung cancer (2011)
  • Author(s): Kijima T, et al.
  • Journal Title: Cancer Science Volume: 102 Issue: 8 Pages: 1602-1604
  • DOI: 10.1111/j.1349-7006.2011.01970.x
  • Peer Reviewed
• [Journal Article] Successful treatment with pemetrexed in a patient with mucinous bronchioloalveolar carcinoma: long-term response duration with mild toxicity (2011)
  • Author(s): Okuda C, et al.
  • Journal Title: Journal of Thoracic Oncology Volume: 6 Issue: 3 Pages: 641-642
  • DOI: 10.1097/jto.0b013e3182037c80
  • Peer Reviewed
• [Journal Article] Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma (2011)
  • Author(s): Takeuchi K, et al
  • Journal Title: Haematologica Volume: 96 Issue: 3 Pages: 464-467
  • DOI: 10.3324/haematol.2010.033514
  • NAID: 40019402944
  • Peer Reviewed
• [Journal Article] Pulmonary inflammatory myofibroblastic tumor expressing a novel fusion, PPFIBP1-ALK: reappraisal of anti-ALK immunohistochemistry as a tool for novel ALK fusion identification (2011)
  • Author(s): Takeuchi K, et al
  • Journal Title: Clinical Cancer Research Volume: 17 Issue: 10 Pages: 3341-3348
  • DOI: 10.1158/1078-0432.ccr-11-0063
  • Peer Reviewed
• [Journal Article] Successful treatment with pemetrexed in a patient with mucinous bronchioloalveolar carcinoma : long-term response duration with mild toxicity. (2011)
  • Author(s): Okuda C, et al.8人中3番目
  • Journal Title: J Thorac Oncol. Volume: 6 Pages: 641-642
  • Peer Reviewed
• [Journal Article] Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma. (2011)
  • Author(s): Takeuchi K, et al.
  • Journal Title: Haematologica. Volume: 96 Pages: 464-467
  • NAID: 40019402944
  • Peer Reviewed
• [Journal Article] Pulmonary inflammatory myofibroblastic tumor expressing a novel fusion, PPFIBP1-ALK : reappraisal of anti-ALK immunohistochemistry as a tool for novel ALK-fusion identification. (2011)
  • Author(s): Takeuchi K, et al.
  • Journal Title: Clin Cancer Res. Volume: 17 Pages: 3341-3348
  • Peer Reviewed
• [Journal Article] EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors (2010)
  • Author(s): Choi, Y. L., Soda, M., et al.(全15名、第3著者)
  • Journal Title: N Engl J Med Volume: 363 Issue: 18 Pages: 1734-1739
  • DOI: 10.1056/nejmoa1007478
  • Peer Reviewed
• [Journal Article] Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma (2010)
  • Author(s): Jokoji R, et al.
  • Journal Title: Journal of Clinical Pathology Volume: 63 Issue: 12 Pages: 1066-1070
  • DOI: 10.1136/jcp.2010.081166
  • Peer Reviewed
• [Journal Article] EML4-ALK fusion in lung (2010)
  • Author(s): Mano H, Takeuchi K
  • Journal Title: American Journal of Pathology Volume: 176 Issue: 3 Pages: 1552-1553
  • DOI: 10.2353/ajpath.2010.091057
  • Peer Reviewed
• [Journal Article] Treatment of lung cancer with an ALK inhibitor after EML4-ALK fusion gene detection using endobronchial ultrasound-guided transbronchial needle aspiration (2010)
  • Author(s): Nakajima T, et al.
  • Journal Title: Journal of Thoracic Oncology Volume: 5 Issue: 12 Pages: 2041-2043
  • DOI: 10.1097/jto.0b013e3181f77b58
  • Peer Reviewed
• [Journal Article] EML4-ALK fusion gene assessment using metastatic lymph node samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (2010)
  • Author(s): Sakairi Y,
  • Journal Title: Clinical Cancer Research Volume: 16 Issue: 20 Pages: 4938-4945
  • DOI: 10.1158/1078-0432.ccr-10-0099
  • Peer Reviewed
• [Journal Article] EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. (2010)
  • Author(s): Choi YL, et al.15人中8番目
  • Journal Title: N Engl J Med. Volume: 363 Pages: 1734-1739
  • Peer Reviewed
• [Journal Article] Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma. (2010)
  • Author(s): Jokoji R, et al.7人中6番目
  • Journal Title: J Clin Pathol. Volume: 63 Pages: 1066-1070
  • Peer Reviewed
• [Journal Article] EML4-ALK fusion in lung. (2010)
  • Author(s): Mano H, Takeuchi K.
  • Journal Title: Am J Pathol. Volume: 176 Pages: 1552-1553
  • Peer Reviewed
• [Journal Article] Treatment of Lung Cancer with an ALK Inhibitor After EML4-ALK Fusion Gene Detection Using Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration. (2010)
  • Author(s): Nakajima T, et al.7人中3番目
  • Journal Title: J Thorac Oncol. Volume: 5 Pages: 2041-2043
  • Peer Reviewed
• [Journal Article] EML4-ALK fusion gene assessment using metastatic lymph node samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration. (2010)
  • Author(s): Sakairi Y, et al.12人中7番目
  • Journal Title: Clin Cancer Res. Volume: 16 Pages: 4938-4945
  • Peer Reviewed
• [Presentation] 新しい肺癌の融合遺伝子 (2013)
  • Author(s): 竹内賢吾
  • Organizer: 第97回日本肺癌学会関西支部会
  • Place of Presentation: 薬業年金会館
  • Year and Date: 2013-02-09
• [Presentation] 病理医による疾患と病因の発見 (2012)
  • Author(s): 竹内賢吾
  • Organizer: 第58回日本病理学会秋期特別総会
  • Place of Presentation: ういんく愛知
  • Year and Date: 2012-11-22
• [Presentation] Novel fusions in lung cancer (2012)
  • Author(s): 竹内賢吾
  • Organizer: 第53回日本肺癌学会
  • Place of Presentation: ホテルグランヴィア岡山
  • Year and Date: 2012-11-09
• [Presentation] ALK fusions (2012)
  • Author(s): 竹内賢吾
  • Organizer: 第53回日本肺癌学会
  • Place of Presentation: ホテルグランヴィア岡山
  • Year and Date: 2012-09-19
• [Presentation] Novel fusion kinases in lung cancer (2012)
  • Author(s): 竹内賢吾
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ホテルロイトン札幌
  • Year and Date: 2012-09-19
• [Presentation] 融合遺伝子の発見 (2012)
  • Author(s): 竹内賢吾
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2012-07-26
• [Presentation] ALK, ROS1, RET融合遺伝子:がんの治療病理学の創成に向けた病理医による新規分子標的の発見 (2012)
  • Author(s): 竹内賢吾
  • Organizer: 第30回日本眼腫瘍学会
  • Place of Presentation: 栃木県総合文化センター
  • Year and Date: 2012-06-30
• [Presentation] ALK, ROS1, RET融合遺伝子:治療病理学の創成に向けた病理医による新規分子標的の同定 (2012)
  • Author(s): 竹内賢吾
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2012-04-27
• [Presentation] ALK肺癌の診断法 (2011)
  • Author(s): 竹内賢吾
  • Organizer: 日本がん分子標的治療学会(JAMTTC)-日本遺伝子診療学会(JSGDT)合同シンポジウム
  • Place of Presentation: 都市センターホテル
  • Year and Date: 2011-12-09
• [Presentation] ALK肺癌の診断法 (2011)
  • Author(s): 竹内賢吾
  • Organizer: 日本がん分子標的治療学会(JAMTTC)-日本遺伝子診療学会合同シンポジウム(JSGDT)
  • Place of Presentation: 都市センターホテル
  • Year and Date: 2011-12-09
• [Presentation] Exploring for ALKoma with use of integrated diagnostic techniques (2011)
  • Author(s): 竹内賢吾
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] Exploring for ALKoma with use of integrated ddiagnostic techniques (2011)
  • Author(s): 竹内賢吾
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] 基礎から学ぶ次世代の分子標的治療薬と基盤技術 (2011)
  • Author(s): 竹内賢吾
  • Organizer: 第9回日本臨床腫瘍学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-07-21
• [Presentation] 未来とは受け入れるものではなく創り出すもの (2011)
  • Author(s): 竹内賢吾
  • Organizer: 第51回日本リンパ網内系学会総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2011-07-01
• [Presentation] シンポジウム2「次世代病理医」 (2011)
  • Author(s): 竹内賢吾
  • Organizer: 第51回日本リンパ網内系学会総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2011-07-01
• [Presentation] Lymphomatoid Gastropathy (2011)
  • Author(s): 竹内賢吾
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-04-30
• [Presentation] 肺癌における組織像・細胞像と遺伝子変化-診断に有用な分子生物学 (2010)
  • Author(s): 竹内賢吾
  • Organizer: 第49回日本臨床細胞学会秋期大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-11-22
• [Presentation] シンポジウム「肺癌における組織像・細胞像と遺伝子変化-診断に有用な分子生物学」 (2010)
  • Author(s): 竹内賢吾
  • Organizer: 第49回日本臨床細胞学会 秋期大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-11-22
• [Presentation] スライドセミナーALK肺癌 (2010)
  • Author(s): 竹内賢吾
  • Organizer: 第28回国際病理学会総会
  • Place of Presentation: ブラジル(サンパウロ)
  • Year and Date: 2010-10-12
• [Presentation] 教育講演(スライドセミナーALK肺癌) (2010)
  • Author(s): 竹内賢吾
  • Organizer: 第28回国際病理学会総会
  • Place of Presentation: ブラジル(サンパウロ)
  • Year and Date: 2010-10-12
• [Presentation] Large B-cell neoplasms(2) (2010)
  • Author(s): 竹内賢吾
  • Organizer: 第50回日本リンパ網内系学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2010-06-18
• [Presentation] シンポジウム「WHOリンパ腫分類第4版の認知、理解、補填」座長・シンポジスト演題3:「Large B-cell neoplasms(2)」 (2010)
  • Author(s): 竹内賢吾
  • Organizer: 第50回日本網内系学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2010-06-18
• [Presentation] Through Microscope to Bench and Bed (2010)
  • Author(s): 竹内賢吾
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2010-04-29
• [Presentation] ALK肺癌:診断法の開発と臨床病理学的特徴 (2010)
  • Author(s): 竹内賢吾
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2010-04-27
• [Presentation] ALK, ROS1, RET融合遺伝子：治療病理学の創成に向けた病理医による新規分子標的の同定
  • Author(s): 竹内 賢吾
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル
  • Invited
• [Presentation] ALK, ROS1, RET融合遺伝子：がんの治療病理学の創成にむけた病理医による新規分子標的の発見
  • Author(s): 竹内 賢吾
  • Organizer: 第30回日本眼腫瘍学会
  • Place of Presentation: 栃木県総合文化センター
  • Invited
• [Presentation] 融合遺伝子の発見
  • Author(s): 竹内 賢吾
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Invited
• [Presentation] Novel fusion Kinases in lung cancer
  • Author(s): 竹内 賢吾
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ホテルロイトン札幌
  • Invited
• [Presentation] ALK fusions
  • Author(s): 竹内 賢吾
  • Organizer: 第53回日本肺癌学会
  • Place of Presentation: ホテルグランヴィア岡山
  • Invited
• [Presentation] Novel fusions in lung cancer
  • Author(s): 竹内 賢吾
  • Organizer: 第53回日本肺癌学会
  • Place of Presentation: ホテルグランヴィア岡山
  • Invited
• [Presentation] 病理医による疾患と病因の発見
  • Author(s): 竹内 賢吾
  • Organizer: 第58回日本病理学会秋期特別総会
  • Place of Presentation: ういんく愛知
• [Presentation] 新しい肺癌の融合遺伝子
  • Author(s): 竹内 賢吾
  • Organizer: 第97回日本肺癌学会 関西支部会
  • Place of Presentation: 薬業年金会館
  • Invited
• [Patent(Industrial Property Rights)] 核酸配列の切断標識方法 (2012)
  • Inventor(s): 竹内賢吾
  • Industrial Property Rights Holder: 公益財団法人がん研究会
  • Filing Date: 2012-08-09