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Investigation of tyrosine kinase gene mutation using real-time PCR assay

Research Project

Project/Area Number 24592097
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Thoracic surgery
Research InstitutionNagoya City University

Principal Investigator

SASAKI Hidefumi  名古屋市立大学, 医学(系)研究科(研究院), 研究員 (00336695)

Co-Investigator(Kenkyū-buntansha) YANO Motoki  名古屋市立大学, 大学院医学研究科, 准教授 (40315833)
OKUDA Katsuhiro  名古屋市立大学, 大学院医学研究科, 助教 (50529170)
矢野 智紀  名古屋市立大学, 医学(系)研究科(研究院), 准教授 (40315883)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
KeywordsBRAF / EGFR / RET / FGFR3 / CAST-PCR / 肺癌 / NTRK1 / RET転座 / 腺癌 / FISH / 免疫染色
Outline of Final Research Achievements

Molecular targeted therapies such as erlotinib or gefitinib that target EGFR mutations and crizotinib that target ALK fusion have demonstrated superior single agent activity in selected patients as compared to standard chemotherapy regimes in lung cancer treatment. Recently, a series of new gene fusions have been described in patients with lung cancer using next generation sequencing. In 2012, we have discovered RET translocation in lung adenocarcinomas. In our cohort, three RET fusion mutants were found. We have developed FISH probes to detect RET translocations. in 2013, we have discovered NTRK1 translocation in lung adenocarcinomas. in 2014, we have discovered FGFR3 translocations in lung adenocarcinomas. In addition, BRAF V600E is a driver mutation that can be effectively targeted with selective BRAF inhibitors. To determine the BRAF mutation status in Japanese lung carcinoma, we investigated BRAF V600E mutations by real time-PCR (CAST-PCR) and immunohistochemical methods.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (22 results)

All 2014 2013 2012

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Identification of recurrent FGFR3-TACC3 fusion oncogenes from lung adenocarcinoma.2014

    • Author(s)
      Capelletti M, Dodge ME, Ercan D, Hammerman PS, Park SI, Kim J, Sasaki H, Jablons DM, Lipson D, Young L, Stephens PJ, Miller VA, Lindeman NI, Munir KJ, Richards WG, Janne PA.
    • Journal Title

      Clin Cancer Res

      Volume: 20 Pages: 6551-6558

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PD-1 gene promoter polymorphisms correlate with a poor prognosis in non-small cell lung cancer.2014

    • Author(s)
      Sasaki H, Tatematsu T, Okuda K, Moriyama S, Yano M, Fujii Y.
    • Journal Title

      Mol Clin Oncol

      Volume: 2 Pages: 1035-1042

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Prognosis of recurrent non-small cell lung cancer following complete resection.2014

    • Author(s)
      Sasaki H, Suzuki A, Tatematsu T, Shitara M, Hikosaka Y, Okuda K, Moriyama S, Yano M, Fujii Y.
    • Journal Title

      Oncol Lett

      Volume: 7 Pages: 1300-1304

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.2013

    • Author(s)
      Vaishnavi A, Capelletti M, Le AT, Kako S, Butaney M, Ercan D, Mahale S, Davies KD, Aisner DL, Pilling AB, Berge EM, Kim J, Sasaki H, Park S, Krykov G, Garraway LA, Hammerman PS, Haas J, Andrews SW, Lipson D, Stephens PJ, Miller VA, Varella-Garcia M, Janne P, Doebele RC.
    • Journal Title

      Nature Medicine

      Volume: 19 Issue: 11 Pages: 1469-1472

    • DOI

      10.1038/nm.3352

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characteristics of lung cancers haboring NRAS mutations2013

    • Author(s)
      Ohashi K, Sequist LV, Arcila ME, Lovly CM, Chen X, Rudin CM, Moran T, Camidge DR, Vnencak-Jones CL, Berry L, Pan Y, Sasaki H, Engelman JA, Garon EB, Dubinett SM, Franklin WA, Riely GJ, Sos ML, Kris MG, Dias-Santagata D, Ladanyi M, Bunn Jr PA, Pao W .
    • Journal Title

      Clinical Cancer Research

      Volume: 19 Issue: 9 Pages: 2584-2591

    • DOI

      10.1158/1078-0432.ccr-12-3173

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Keap1 mutations in lung cancer patients.2013

    • Author(s)
      Sasaki H, Suzuki A, Shitara M, Okuda K, Hikosaka Y, Moriyama S, Yano M, Fujii Y.
    • Journal Title

      Oncol Lett

      Volume: 6 Pages: 719-721

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genotype analysis of the NRF2 gene mutation in lung cancer2013

    • Author(s)
      Sasaki H, Suzuki A, Shitara M, Hikosaka Y, Okuda K, Moriyama S, Yano M, Fujii Y
    • Journal Title

      Int J Mol Med

      Volume: 31 Issue: 5 Pages: 1135-1138

    • DOI

      10.3892/ijmm.2013.1324

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] RET expression and detection of KIF5B/RET gene arrangements in Japanese lung cancer.2012

    • Author(s)
      Sasaki H, Shimizu S, TaniY, Maekawa M, Okuda K, Yokota K, Shitara M, Hikosaka Y, Moyiyama S, Yano Met al.
    • Journal Title

      Cancer Medicine

      Volume: 1 Pages: 1167-1170

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Polymorphisms in intron 1 of the EGFR gene in non-small cell lung cancer patients.2012

    • Author(s)
      Shitara M, Sasaki H, Yokota K, Okuda K, Hikosaka Y, Moriyama S, Yano M, et al
    • Journal Title

      Exp Ther Med

      Volume: 4 Pages: 785-789

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung2012

    • Author(s)
      Yokota K, Sasaki H, Okuda K, Shimizu S, Shitara M, Hikosaka Y, Moriyama S, Yano M, Fujii Y
    • Journal Title

      Oncol Rep

      Volume: 28(4) Issue: 4 Pages: 1187-1192

    • DOI

      10.3892/or.2012.1908

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Angiopoietin-like protein ANGPTL2 gene expression is correlated with lymph node metastasis in lung cancer.2012

    • Author(s)
      Sasaki H, Suzuki A, Shitara M, Hikosaka Y,Okuda K, Moriyama S, Yano M, Fujii Y.
    • Journal Title

      Oncol Lett

      Volume: 4 Pages: 1325-1328

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of thymidylate synthase and orotate phosphoribosyltransferase in thymic carcinoma2012

    • Author(s)
      Yokota K, Sasaki H, Okuda K, Shitara M, Hikosaka Y, Moriyama S, Yano M, Fujii Y
    • Journal Title

      Exp Ther Med

      Volume: 4 Pages: 589-593

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 肺腺癌患者における新規RITおよびARAF遺伝子変異検索と新たな転座遺伝子検索2014

    • Author(s)
      佐々木秀文、立松勉、奥田勝裕、羽田裕司、森山悟、矢野智紀、藤井義敬
    • Organizer
      第55回日本肺癌学会学術総会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-11-15 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肺癌におけるBRAF V600E遺伝子変異のintra-tumor heterogeneityに関する検討2014

    • Author(s)
      立松勉、佐々木秀文、奥田勝裕、羽田裕司、森山悟、矢野智紀、藤井義敬、清水重喜
    • Organizer
      第55回日本肺癌学会学術総会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-11-15 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肺癌における新規599T挿入変異とダコエンビジョンフレックス系を用いたV600E抗体による免疫組織学的検索2013

    • Author(s)
      佐々木秀文, 奥田勝裕, 森山 悟, 矢野智紀, 藤井義敬
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] Dako Envision FLEXとBRAFV600E特異的抗体を用いた肺癌におけるBRAF遺伝子変異免疫組織学的検索2013

    • Author(s)
      佐々木秀文, 設楽将之, 奥田勝裕, 彦坂 雄, 森山 悟, 矢野智紀, 藤井義敬
    • Organizer
      第66回日本胸部外科学会定期学術集会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] 当院における非小細胞肺癌治癒切除後再発例の予後因子の解析~EGFRTKIの使用が及ぼす影響2013

    • Author(s)
      佐々木秀文, 立松勉、設楽将之, 奥田勝裕, 彦坂 雄, 森山 悟, 矢野智紀, 藤井義敬
    • Organizer
      第54回日本肺癌学会総会
    • Place of Presentation
      ホテルニューオータニ(東京)
    • Related Report
      2013 Research-status Report
  • [Presentation] KIF5B/RET fusion gene in surgically-treated Japanese adenocarcinoma of the lung2013

    • Author(s)
      Hidefumi Sasaki, Shigeki Shimizu, Yoichi Tani, Katsuhiro Okuda, Yu Hikosaka, Satoru Moriyama, Motoki Yano, and Yoshitaka Fujii
    • Organizer
      15thWorld Conference on Lung Cancer
    • Place of Presentation
      Sydney Convention & Exhibition Centre, Sydney, Australia
    • Related Report
      2013 Research-status Report
  • [Presentation] Discovery of recurrent KIF5B-RET fusions and other targetable alterations from clinical NSCLC specimens.2012

    • Author(s)
      Capelletti M, Lipson M, Otto G, Yelensky R, Ercan D, Kim J, Sasaki H, et al
    • Organizer
      2012 ASCO annual meeting
    • Place of Presentation
      Chicago McCormick Place (アメリカ)
    • Related Report
      2012 Research-status Report
  • [Presentation] Characteristics of NSCLCs haboring NRAS mutations.2012

    • Author(s)
      Ohashi K, Sequist LV, Sos M, Chen X, Rudin CM, Moran T, Arcia ME, Loyly CM, Vnencak-Jones CL, Sasaki H, et al
    • Organizer
      2012 ASCO annual meeting
    • Place of Presentation
      Chicago McCormick Place (アメリカ)
    • Related Report
      2012 Research-status Report
  • [Presentation] Identification of recurrent oncogenic KIF5B-RET rearrangements in non-small cell lung cancer.2012

    • Author(s)
      Capelletti M, Lipson D, Otto G, Yelensky R, Ercan D, Kim J, Sasaki H, et al.
    • Organizer
      AACR 103th annual meeting.
    • Place of Presentation
      Chicago McCormick Place (アメリカ)
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] KIF5B遺伝子とRET遺伝子との間の転座を検出するFISHアッセイ2013

    • Inventor(s)
      佐々木秀文
    • Industrial Property Rights Holder
      佐々木秀文
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-01-18
    • Related Report
      2012 Research-status Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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