Establishment of novel assay methods for translocation type gene alterations.

• Project/Area Number: 25670183
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: YATABE Yasushi 愛知県がんセンター(研究所), 分子腫瘍学部, 研究員 (90280809)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 遺伝子転座 / 検出法 / がん組織

Outline of Final Research Achievements

EML4 is transcriptionally active, but not ALK in the normal lung, and EML4-ALK translocation in lung cancer leads to activate the transcription of ALK kinase by the EML4 promoter. Therefore, ALK transcription has different patterns between 5’ and 3’ ends when the tumor has the translocation, and the difference can be utilized for a screening tool for the translocation. We examined 15 and 40 of ALK rearranged and wild type tumors, respectively, and found this method could work well with quantitative RT-PCR. Similarly, we applied this method to ROS and RET translocations, but the gene was expressed in the normal lung tissues. So, we defined the appropriate cut-off values, and also found the method could be used as a screening. Furthermore, we established immunohistochemistry to detect ROS1-rearranged tumors, and reported the results (Clin Lung Cancer 2015).

Research Products

• [Journal Article] ROS1 Immunohistochemistry Among Major Genotypes of Non-Small-Cell Lung Cancer (2014)
  • Author(s): Boyle, Theresa A Masago, Katsuhiro Ellison, Kim E Yatabe, Yasushi Hirsch, Fred R
  • Journal Title: Clin Lung Cancer Volume: 16 Issue: 2 Pages: 106-11
  • DOI: 10.1016/j.cllc.2014.10.003
  • Peer Reviewed
• [Journal Article] An International Interpretation Study Using the Alk Ihc Antibody D5f3 and a Sensitive Detection Kit Demonstrates High Concordance between Alk Ihc and Alk Fish and between Evaluators. (2014)
  • Author(s): Wynes MW, Sholl LM, Dietel M, Schuuring E, Tsao MS, Yatabe Y, Tubbs RR, Hirsch FR
  • Journal Title: J Thorac Oncol. Volume: 9 Issue: 5 Pages: 631-8
  • DOI: 10.1097/jto.0000000000000115
  • Peer Reviewed
• [Journal Article] Solitary Pulmonary Metastasis from Lung Cancer Harboring Eml4-Alk after a 15-Year Disease-Free Interval. (2013)
  • Author(s): Tomizawa K, Ito S, Suda K, Fukui T, Usami N, Hatooka S, Kuwano H, Yatabe Y, Mitsudomi T.
  • Journal Title: Lung Cancer. Volume: 80 Issue: 1 Pages: 99-101
  • DOI: 10.1016/j.lungcan.2012.12.011
  • Peer Reviewed
• [Journal Article] Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. (2013)
  • Author(s): Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, Ishikawa Y, Wistuba I, Flieder DB, Franklin W, Gazdar A, Hasleton PS, Henderson DW, Kerr KM, Petersen I, Roggli V, Thunnissen E and Tsao M.
  • Journal Title: Arch Pathol Lab Med. Volume: 137 Issue: 5 Pages: 668-84
  • DOI: 10.5858/arpa.2012-0263-ra
  • Peer Reviewed
• [Presentation] Yasushi IHC proposal to IASLC path panel (2015)
  • Author(s): Yasushi Yatabe
  • Organizer: IASLC pathology committee
  • Place of Presentation: ハインズコンベンションセンター米国ボストン
  • Year and Date: 2015-03-20
• [Presentation] Molecular testing for EGFR/ALK (2013)
  • Author(s): Yasushi Yatabe
  • Organizer: 8th Asia Pacific IAP Congress
  • Place of Presentation: Pusan, Korea
  • Invited
• [Presentation] Molecular Testing (2013)
  • Author(s): Yasushi Yatabe
  • Organizer: Pulmonary Pathology Society
  • Place of Presentation: Grenoble, France
  • Invited