Molecular analyses of EML-ALK-positive lung cancer

2010 Fiscal Year Final Research Report

• Project/Area Number: 21689023
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Jichi Medical University
• Principal Investigator: SODA Manabu Jichi Medical University, 医学部, 研究員 (10406118)
• Project Period (FY): 2009 – 2010
• Keywords: EML4-ALK / 肺がん / 遺伝子診断

Research Abstract

We discovered in 2007 that a chromosomal rearrangement inv(2)(p21p23) in lung cancer generates a novel oncogene EML4-ALK which produces a constitutively activated, fusion protein between the amino-terminal half of a microtubule-associated protein EML4 and the catalytic domain of ALK. Clinical trials with ALK inhibitors are ongoing worldwide, and one of such early trials has already proved a marked efficacy of the compound against EML4-ALK-positive lung cancer. The swift introduction of ALK inhibitors to clinics raises a concern as to how EML4-ALK-positive tumors are diagnosed both accurately and sensitively. Here we developed multiplex RT-PCR system to capture EML4-ALK cDNAs, and further proved such technology to be a reliable means for clinical use.

Research Products

• [Journal Article] Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma. (2011)
  • Author(s): Takeuchi K, Soda M, Togashi Y, Ota Y, Sekiguchi Y, Hatano S, Asaka R, Noguchi M, Mano H.
  • Journal Title: Haematologica 96 Pages: 464-467
• [Journal Article] Array-based genomic resequencing of human leukemia. (2010)
  • Author(s): Yamashita Y, Yuan J, Suetake I, Suzuki H, Ishikawa Y, Choi YL, Ueno T, Soda M, Hamada T, Haruta H, Takada S, Miyazaki Y, Kiyoi H, Ito E, Naoe T, Tomonaga M, Toyota M, Tajima S, Iwama A, Mano H.
  • Journal Title: Oncogene 29 Pages: 3723-3731
• [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, Nakajima T, Yasufuku K, Ikebe D, Kageyama H, Soda M, Takeuchi K, Itami M, Iizasa T, Yoshino I, Mano H, Kimura H.
  • Journal Title: Clin Cancer Res 16 Pages: 4938-4945
• [Journal Article] Incidentally proven pulmonary "ALKoma". (2010)
  • Author(s): Osoegawa A, Nosaki K, Miyamoto H, Kometani T, Hirai F, Ondo K, Seto T, Sugio K, Choi YL, Soda M, Mano H, Ichinose Y.
  • Journal Title: Intern Med 49 Pages: 603-606
• [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, Kimura H, Takeuchi K, Soda M, Mano H, Yasufuku K, Iizasa T.
  • Journal Title: J Thorac Oncol 5 Pages: 2041-2043
• [Journal Article] Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening. (2010)
  • Author(s): Hatanaka H, Tsukui M, Takada S, Kurashina K, Choi YL, Soda M, Yamashita Y, Haruta H, Hamada T, Ueno T, Tamada K, Hosoya Y, Sata N, Yasuda Y, Nagai H, Sugano K, Mano H.
  • Journal Title: Cancer Sci 101 Pages: 54-59
• [Journal Article] Identification of the transforming activity of Indian hedgehog by retroviral expression screening. (2010)
  • Author(s): Hatanaka H, Takada S, Tsukui M, Choi YL, Kurashina K, Soda M, Yamashita Y, Haruta H, Hamada T, Tamada K, Hosoya Y, Sata N, Nagai H, Yasuda Y, Sugano K, Mano H.
  • Journal Title: Cancer Sci 101 Pages: 60-64
• [Journal Article] EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. (2010)
  • Author(s): Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H.
  • Journal Title: N Engl J Med 363 Pages: 1734-1739
• [Journal Article] Screening for genetic abnormalities involved in ovarian carcinogenesis using retroviral expression libraries. (2009)
  • Author(s): Wada T, Yamashita Y, Saga Y, Takahashi K, Koinuma K, Choi YL, Kaneda R, Fujiwara S, Soda M, Watanabe H, Kurashina K, Hatanaka H, Enomoto M, Takada S, Mano H, Suzuki M.
  • Journal Title: Int J Oncol 35 Pages: 973-976
• [Journal Article] KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. (2009)
  • Author(s): Takeuchi K, Choi YL, Togashi Y, Soda M, Hatano S, Inamura K, Takada S, Ueno T, Yamashita Y, Satoh Y, Okumura S, Nakagawa K, Ishikawa Y, Mano H.
  • Journal Title: Clin Cancer Res 15 Pages: 3143-3149
• [Journal Article] EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset. (2009)
  • Author(s): Inamura K, Takeuchi K, Togashi Y, Hatano S, Ninomiya H, Motoi N, Mun MY, Sakao Y, Okumura S, Nakagawa K, Soda M, Choi YL, Mano H, Ishikawa Y.
  • Journal Title: Mod Pathol 22 Pages: 508-515
• [Presentation] 肺癌の分子標的治療基礎から臨床へ非小細胞肺がんにおけるALK融合遺伝子検出法 (2010)
  • Author(s): 曽田学, 間野博行
  • Organizer: 第50回日本肺癌学会総会
  • Place of Presentation: 広島
  • Year and Date: 20101103-20101104
• [Presentation] 肺がんにおける新規がん遺伝子EML4-ALKの発見(Discovery of EML4-ALK oncogene ; an effective target in lung cancer) (2010)
  • Author(s): 曽田学, 間野博行
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-20100924
• [Presentation] A Japanese nationwide network for the diagnosis of EML4-ALK-positive lung cancer : A joint study of ALCAS and NEJ004 (2010)
  • Author(s): Manabu Soda, Hiroyuki Mano, et al.
  • Organizer: ASCO Annual Meeting 2010
  • Place of Presentation: アメリカ,シカゴ
  • Year and Date: 20100604-20100608
• [Presentation] Multiplex RT-PCR法によるALK融合型がん遺伝子の診断;ALK-lung cancer study group (ALCAS)診断ネットワークの中間報告 (2010)
  • Author(s): 曽田学、間野博行
  • Organizer: 第50回日本呼吸器学会学術講演会
  • Year and Date: 20100423-20100425
• [Presentation] EML4-ALK fusion-type protein tyrosine kinase in lung cancer (2010)
  • Author(s): Manabu Soda, Toshihide Ueno, Yoshihiro Yamashita, Hiroyuki Mano.
  • Organizer: Keystone Symposia
  • Place of Presentation: カナダ,ビクトリア
  • Year and Date: 20100323-20100328
• [Presentation] ALK-positive Lung Cancer : Discovery of EML4-ALK Fusion Tyrosine Kinase (2010)
  • Author(s): Manabu Soda
  • Organizer: 6^<th> Tucson Symposium
  • Place of Presentation: アメリカ,ツーソン
  • Year and Date: 20100310-20100311
• [Presentation] ALCAS診断ネットワークの中間報告-multiplex RT-PCR法による診断- (2009)
  • Author(s): 曽田学、杉山幸比古、間野博行
  • Organizer: 第50回日本肺癌学会総会
  • Place of Presentation: 東京
  • Year and Date: 20091112-20091113
• [Presentation] EML4-ALK fusion-type protein tyrosine kinase in carcinogenesis (2009)
  • Author(s): 曽田学
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20091001-20091003
• [Presentation] 肺がんにおける新規融合型がん遺伝子EML4-ALKの発見 (2009)
  • Author(s): 曽田学
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 20090612-20090614
• [Presentation] Analysis of a Mouse Model for EML4-ALK-Positive Lung Cancer (2009)
  • Author(s): Manabu Soda, Shuji Takada, Kengo Takeuchi, Yuichi Ishikawa, Yukihiko Sugiyama, Hiroyuki Mano.
  • Organizer: ATS 2009 International Conference
  • Place of Presentation: アメリカ,サンディエゴ
  • Year and Date: 20090515-20090520
• [Presentation] An experimental model for in vivotreatment with ALK inhibitors of EML4-ALK-positive lung cancer (2009)
  • Author(s): Manabu Soda, Shuji Takada, Kengo Takeuchi, Hisashi Hatanaka, Yoshihiro Yamashita, Yuichi Ishikawa, Yukihiko Sugiyama, Hiroyuki Mano.
  • Organizer: AACR 100th Annual Meeting 2009
  • Place of Presentation: アメリカ,デンバー
  • Year and Date: 20090418-20090422
• [Remarks] ホームページ等 なし