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

• Project/Area Number: 24592097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Nagoya 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: ¥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)
• Keywords: BRAF / 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.

Research Products

• [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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Characteristics of lung cancers haboring NRAS mutations (2013)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Genotype analysis of the NRF2 gene mutation in lung cancer (2013)
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung (2012)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Expression of thymidylate synthase and orotate phosphoribosyltransferase in thymic carcinoma (2012)
  • 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
  • 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
• [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
• [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）
• [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）
• [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）
• [Presentation] KIF5B/RET fusion gene in surgically-treated Japanese adenocarcinoma of the lung (2013)
  • 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
• [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）
• [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）
• [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）
• [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
  • Overseas