Analysis of molecular oncogenesis for lung cancer with fusion kinases

• Project/Area Number: 22300326
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: SAI Eirin 東京大学, 大学院・医学系研究科, 特任准教授 (40458295)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2010: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: がん遺伝子 / 肺がん

Research Abstract

In 2007, we discovered the EML4-ALK fusion-type oncogene in lung cancer, and aspecific inhibitor against ALK kinase is already approved and used as a therapeuticdrug. Here we examined lung cancer specimens before and after relapse against theALK inhibitor treatment, and have identified secondary mutations within EML4-ALK thataccount for drug resistance. Further, we established multiplex RT-PCR system for thediagnosis of EML4-ALK-positive lung cancer, and confirmed its reliability in a largescale Japanese cohort.

Research Products

• [Journal Article] (2013)
  • Author(s): Kawazu M, Ueno T, Kontani K, Ogita Y, Ando M, Fukumura K, Yamato A, Soda M, Takeuchi K, Miki Y, Yamaguchi H, Yasuda T, Naoe T,Yamashita Y, Katada T, Choi YL, Mano H,
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110 Issue: 8 Pages: 3029-3034
  • DOI: 10.1073/pnas.1216141110
  • Peer Reviewed
• [Journal Article] Oncogenic MAP2K1 mutations in human epithelial tumors (2012)
  • Author(s): Choi, Y. L., Soda, M., et al.(全11名、第10著者)
  • Journal Title: Carcinogenesis Volume: 33 Issue: 5 Pages: 956-961
  • DOI: 10.1093/carcin/bgs099
  • 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] 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] High-throughput resequencing of target-captured cDNA in cancer cells (2012)
  • Author(s): Ueno, T., Yamashita, Y., et al.(全9名、第2著者)
  • Journal Title: Cancer science Volume: 103 Issue: 1 Pages: 131-135
  • DOI: 10.1111/j.1349-7006.2011.02105.x
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): Sasaki D, Imaizumi Y, Hasegawa H, Osaka A, Tsukasaki K, Choi YL, Mano H, Marquez VE,Hayashi T, Yanagihara K, Moriwaki Y,Miyazaki Y, Kamihira S, Yamada Y,
  • Journal Title: Haematologica Volume: 96 Issue: 5 Pages: 712-719
  • DOI: 10.3324/haematol.2010.028605
  • Peer Reviewed
• [Journal Article] MCPIP1はDicerに拮抗してmicroRNAのプロセシングを阻害する (2011)
  • Author(s): 鈴木洋
  • Journal Title: Mol Cell Volume: 44 Issue: 3 Pages: 424-436
  • DOI: 10.1016/j.molcel.2011.09.012
  • Peer Reviewed
• [Journal Article] Overexpression of enhancer of zeste homolog 2 with trimethylation of lysine 27 on histone H3 in adult T-cell leukemia/lymphoma as a target for epigenetic therapy (2011)
  • Author(s): Sasaki D, et al.
  • Journal Title: Haematologica Volume: (オンライン)
  • 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] Identification of the transforming activity of Indian hedgehog by retroviral expression screening (2010)
  • Author(s): Hatanaka, H., Takada, S., et al.(全16名、第7著者)
  • Journal Title: Cancer science Volume: 101 Issue: 1 Pages: 60-64
  • DOI: 10.1111/j.1349-7006.2009.01355.x
  • Peer Reviewed
• [Journal Article] Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening (2010)
  • Author(s): Hatanaka, H., Tsukui, M., et al.(全17名、第7著者)
  • Journal Title: Cancer science Volume: 101 Issue: 1 Pages: 54-59
  • DOI: 10.1111/j.1349-7006.2009.01348.x
  • Peer Reviewed
• [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: Internal Medicine Volume: 49 Issue: 6 Pages: 603-606
  • DOI: 10.2169/internalmedicine.49.3126
  • NAID: 130000251770
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Array-based genomic resequencing of human leukemia (2010)
  • Author(s): Yamashita Y, Yuan J, Suetake I, Suzuki H, Ishikawa Y, Choi Y L, 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, and Mano H
  • Journal Title: Oncogene Volume: 29 Issue: 25 Pages: 3723-3731
  • DOI: 10.1038/onc.2010.117
  • Peer Reviewed
• [Journal Article] EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors (2010)
  • Author(s): Choi YL, et al.
  • Journal Title: New England Journal of Medicine Volume: 363 Pages: 1734-1739
  • Peer Reviewed
• [Journal Article] Array-based genomic resequencing of human leukemia (2010)
  • Author(s): Yamashita Y, et al.
  • Journal Title: Oncogene Volume: 29 Pages: 3723-3731
  • Peer Reviewed
• [Presentation] ALK チロシンキナーゼ阻害剤耐性獲得機構の解明 (2011)
  • Author(s): 崔 永林
  • Organizer: 第70回日本癌学会学術集会
  • Place of Presentation: 名古屋