Detection of EML4-ALK in serum RNA from lung cancer patients

• Project/Area Number: 24701013
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnosis
• Research Institution: Kinki University
• Principal Investigator: SAKAI Kazuko 近畿大学, 医学部, 助教 (20580559)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 薬効評価と予測 / ＥＭＬ４－ＡＬＫ / 血清 / バイオマーカー

Research Abstract

The presence of the transforming fusion gene EML4-ALK in non–small cell lung cancer (NSCLC) is a predictive marker for the efficacy of ALK kinase inhibitors. Circulating RNA in serum is an emerging field for noninvasive molecular diagnosis. We designed EML4-ALK detection assay using PCR-based MassARRAY platform. We attempted a RNA extraction method, primer design, and reverse transcription reagents to optimize our detection system with serum samples. We evaluated whether EML4-ALK fusion RNA could be detected in serum obtained from 12 NSCLC patients with ALK rearrangements. The EML4-ALK RNA (variant 1 and 3) was detected in serum from 2 of 12 patients. The detection of EML4-ALK in serum RNA samples by MassARRAY assay is feasible. This noninvasive assay will be useful in patients with insufficient or unavailable tumor specimens. Additional experiments will reveal the sensitivity and specificity of this detection system.

Research Products

• [Journal Article] Detection of EGFR T790M mutation in plasma DNA from patients (2013)
  • Author(s): Sakai, K., Horiike, A., Darryl, I., Keita, K., Fujita, Y., Tanimoto, A., Sakatani, T., Saito, R., Kaburaki, K., Noriko, Y., Ohyanagi, F., Nishio, M., Nishio, K.
  • Journal Title: Cancer Sci Volume: 104(9) Pages: 1198-204
  • Peer Reviewed
• [Journal Article] Detection of EGFR T790M mutation in plasma DNA from patients refractory to EGFR tyrosine kinase inhibitor. (2013)
  • Author(s): Sakai, K., Horiike, A., Darryl, I., Keita, K., Fujita, Y., Tanimoto, A., Sakatani, T., Saito, R., Kaburaki, K., Noriko, Y., Ohyanagi, F., Nishio, M., Nishio, K.
  • Journal Title: Cancer Sci. Volume: 104(9) Issue: 9 Pages: 1198-204
  • DOI: 10.1111/cas.12211
  • Peer Reviewed
• [Journal Article] Clinical outcome for EML4-ALK-positive patients with advanced non-small-cell lung cancer treated with first-line platinum-based chemotherapy (2012)
  • Author(s): Takeda, M., Okamoto, I., Sakai, K., Kawakami, H., Nishio, K., Nakagawa, K.
  • Journal Title: Ann Oncol Volume: 23(11) Pages: 2931-6
  • Peer Reviewed
• [Journal Article] A novel mass spectrometry-based assay for EML4 exon 13 ALK exon 20 EML4 exon 6 ALK exon 20 diagnosis of EML4-ALK-positive non-small cell lung cancer (2012)
  • Author(s): Sakai, K., Okamoto, I., Takezawa, K., Hirashima, T., Kaneda, H., Takeda, M., Matsumoto, K., Kimura, H., Fujita, Y., Nakagawa, K., Arao, T., Nishio, K.
  • Journal Title: J Thorac Oncol Volume: 7(5) Pages: 913-8
  • Peer Reviewed
• [Journal Article] A novel mass spectrometry-based assay for diagnosis of EML4-ALK-positive non-small cell lung cancer (2012)
  • Author(s): Sakai K. et al
  • Journal Title: J Thorac Oncol Volume: 7 Issue: 5 Pages: 913-8
  • DOI: 10.1097/jto.0b013e31824c7f7a
  • Peer Reviewed
• [Journal Article] Clinical outcome for EML4-ALK-positive patients with advanced non-small-cell lung cancer treated with first-line platinum-based chemotherapy. (2012)
  • Author(s): Takeda M.
  • Journal Title: Ann Oncol Volume: 23(11) Issue: 11 Pages: 2931-6
  • DOI: 10.1093/annonc/mds124
  • Peer Reviewed
• [Presentation] Detection of EGFR T790M mutation in plasma DNA from patients refractory to EGFR tyrosine kinase inhibitor (2013)
  • Author(s): Sakai, K., Horiike, A., Darryl, I., Keita, K., Fujita, Y., Tanimoto, A., Sakatani, T., Saito, R., Kaburaki, K., Noriko, Y., Ohyanagi, F., Nishio, M., Nishio, K.
  • Organizer: The 11th Annual Meeting of Japanese Society of Medical Oncology
  • Place of Presentation: Sendai, JAPAN
• [Presentation] Detection of EGFR T790M mutation in plasma DNA from patients refractory to EGFR tyrosine kinase inhibitor. (2013)
  • Author(s): Sakai, K., Horiike, A., Darryl, I., Keita, K., Fujita, Y., Tanimoto, A., Sakatani, T., Saito, R., Kaburaki, K., Noriko, Y., Ohyanagi, F., Nishio, M., Nishio, K.
  • Organizer: The 11th Annual Meeting of Japanese Society of Medical Oncology
  • Place of Presentation: 仙台国際センター
• [Presentation] A novel mass spectrometry-based assay for diagnosis of EML4-ALK-positive non-small cell lung cancer (2012)
  • Author(s): Sakai, K., Okamoto, I., Takezawa, K., Hirashima, T., Kaneda, H., Takeda, M., Matsumoto, K., Kimura, H., Fujita, Y., Nakagawa, K., Arao, T., Nishio, K.
  • Organizer: The 10th Annual Meeting of Japanese Society of Medical Oncology
  • Place of Presentation: Osaka, JAPAN
• [Presentation] Detection of EML4-ALK in serum RNA from lung cancer patients using MassARRAY platform (2012)
  • Author(s): Kudo, K., Nishio, M., Sakai, K., Tanimoto, A., Sakatani, T., Saito, R., Kaburaki, K., Yanagitani, N., Horiike, A., Ohyanagi, F., Nishio, K.
  • Organizer: ASCO annual Meeting
  • Place of Presentation: Chicago, USA
• [Presentation] Detection of EML4-ALK in serum RNA from lung cancer patients using MassARRAY platform (2012)
  • Author(s): Kudo K. et al
  • Organizer: 2012 ASCO Annual Meeting
  • Place of Presentation: Chicago, USA