Molecular profiling and biomarker study of thoracic malignancies

• Project/Area Number: 24591186
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Wakayama Medical University (2013-2014); Shizuoka Cancer Center Research Institute (2012)
• Principal Investigator: YAMAMOTO Nobuyuki 和歌山県立医科大学, 医学部, 教授 (60298966)
• Co-Investigator(Kenkyū-buntansha): KOH Yasuhiro 和歌山県立医科大学, 医学部, 講師 (80426519) ; SERIZAWA Masakuni 静岡県立静岡がんセンター研究所, 新規薬剤開発・評価研究部, 研究員 (00569915)
• Co-Investigator(Renkei-kenkyūsha): KONDO Haruhiko 杏林大学, 呼吸器・甲状腺外科, 教授 (60399590) ; ENDO Masahiro 静岡県立静岡がんセンター, 画像診断科, 部長 ; NAKAJIMA Takashi 静岡県立静岡がんセンター, 病理診断科, 部長 (20124422)
• 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 遺伝子異常 / バイオバンク / 分子標的治療 / 遺伝子変異 / 肺癌

Outline of Final Research Achievements

In this project, we established a biobank system of specimens from patients with thoracic malignancies. We conducted tumor genotyping study using tissue samples obtained from the biobank to detect 23 hotspot mutations in 9 cancer-related genes. In adenocarcinoma, EGFR mutation was most frequently detected (35.0%) followed by KRAS mutation (8.5%) and ALK translocation (5.0%). On the other hand, in small-cell lung cancer and squamous cell lung cancer, mutation rate was much lower than that in adenocarcinoma, suggesting driver mutations are rarely detected in those histologic types. We also established genotyping platform utilizing next-generation sequencing technologies for more comprehensive mutational analysis.

Research Products

• [Journal Article] Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays. (2014)
  • Author(s): Hirotsugu Kenmotsu
  • Journal Title: BMC Cancer Volume: 14 Issue: 1 Pages: 786-786
  • DOI: 10.1186/1471-2407-14-786
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of actionable mutations in malignant pleural mesothelioma (2014)
  • Author(s): Takehito Shukuya
  • Journal Title: Lung Cancer Volume: 86 Issue: 1 Pages: 35-40
  • DOI: 10.1016/j.lungcan.2014.08.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mutant allele frequency predicts the efficacy of EGFR-TKIs in lung adenocarcinoma harboring the L858R mutation (2014)
  • Author(s): Akira Ono
  • Journal Title: Annals of Oncology Volume: 25 Issue: 10 Pages: 1948-1953
  • DOI: 10.1093/annonc/mdu251
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Changes in forced expiratory volume in 1 second over time in patients with controlled asthma at baseline (2014)
  • Author(s): Kazuto Matsunaga
  • Journal Title: Respiratory Medicine Volume: 108 Issue: 7 Pages: 976-982
  • DOI: 10.1016/j.rmed.2014.04.014
  • Peer Reviewed
• [Journal Article] Multiplexed molecular profiling of lung cancer using pleural effusion (2014)
  • Author(s): Hiroaki Akamatsu
  • Journal Title: Journal of Thoracic Oncology Volume: 9 Issue: 7 Pages: 1048-1052
  • DOI: 10.1097/jto.0000000000000203
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Assessment of mutational profile of Japanese lung adenocarcinoma patients by multitarget assays: A prospective, single-institute study (2014)
  • Author(s): Masakuni Serizawa
  • Journal Title: Cancer Volume: in press Issue: 10 Pages: 1471-1481
  • DOI: 10.1002/cncr.28604
  • Peer Reviewed
• [Journal Article] Molecular profiling of small cell lung cancer in a Japanese cohort. (2014)
  • Author(s): Kazushige Wakuda
  • Journal Title: Lung Cancer Volume: 84 Issue: 2 Pages: 139-144
  • DOI: 10.1016/j.lungcan.2014.02.013
  • 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
  • Journal Title: Cancer Sci Volume: 104 Issue: 6 Pages: 1198-204
  • DOI: 10.1111/cas.12411
  • Peer Reviewed
• [Journal Article] Genomic aberrations associated with erlotinib resistance in non-small cell lung cancer cells (2013)
  • Author(s): Masakuni Serizawa
  • Journal Title: Anticancer Research Volume: 33 Pages: 5223-33
  • Peer Reviewed
• [Journal Article] The effect of CYP2C19 polymorphism on the safety, tolerability, and pharmacokinetics of tivantinib (ARQ 197): results from a phase I trial in advanced solid tumors (2013)
  • Author(s): Nobuyuki Yamamoto
  • Journal Title: Annals of Oncology Volume: 24 Issue: 6 Pages: 1653-1659
  • DOI: 10.1093/annonc/mdt014
  • Peer Reviewed
• [Journal Article] CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study (2013)
  • Author(s): Takashi Seto
  • Journal Title: Lancet Oncology Volume: 14 Issue: 7 Pages: 590-8
  • DOI: 10.1016/s1470-2045(13)70142-6
  • Peer Reviewed
• [Journal Article] Combined treatment with erlotinib and a transforming growth factor-β type I receptor inhibitor effectively suppresses the enhanced motility of erlotinib-resistant non-small cell lung cancer cells (2013)
  • Author(s): Masakuni Serizawa
  • Journal Title: Journal of Thoracic Oncology Volume: 8 Issue: 3 Pages: 259-69
  • DOI: 10.1097/jto.0b013e318279e942
  • Peer Reviewed
• [Journal Article] The Impact of Clinical Outcomes According to EGFR Mutation Status in Patients with Locally Advanced Lung Adenocarcinoma Who Recieved Concurrent Chemoradiotherapy (2013)
  • Author(s): Hiroaki Akamatsu
  • Journal Title: American Journal of Clinical Oncology Volume: Epub ahead of print Issue: 2 Pages: 144-147
  • DOI: 10.1097/coc.0b013e31826e04f9
  • Peer Reviewed
• [Journal Article] A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer. (2013)
  • Author(s): Kurahashi, I., Fujita, Y., Arao, T., Kurata, T., Koh, Y., Sakai, K., Matsumoto, K., Tanioka, M., Takeda, K., Takiguchi, Y., Yamamoto, N., Tsuya, A., Matsubara, N., Mukai, H., Minami, H., Chayahara, N., Yamanaka, Y., Miwa, K., Takahashi, S., Takahashi, S., Nakagawa, K. and Nishio, K.
  • Journal Title: PloS one Volume: 8 Issue: 5 Pages: e63249-e63249
  • DOI: 10.1371/journal.pone.0063249
  • Peer Reviewed
• [Presentation] BevacizumabとEGFR-TKIとの併用: Erlotinib+Bevacizumab vs Erlotinibのrandomized phaseⅡ studyの経験から (2014)
  • Author(s): 山本信之
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-16
  • Invited
• [Presentation] 抗がん剤の副作用対策の現状と問題点 (2013)
  • Author(s): 山本信之
  • Organizer: 第40回日本毒性学会学術年会
  • Place of Presentation: 千葉市
  • Invited
• [Presentation] 肺腺癌における個別化医療の推進を目的とした体細胞変異プロファイリング (2013)
  • Author(s): 芹澤昌邦
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Invited
• [Presentation] 肺扁平上皮癌における遺伝子プロファイリング (2013)
  • Author(s): 釼持広知
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Invited
• [Presentation] Identification of actionable mutations in surgically resected tumor specimens from Japanese patients with non-small cell lung cancer by ultra-deep targeted sequencing (2013)
  • Author(s): Yasuhiro Koh
  • Organizer: 49th American Society of Clinical Oncology
  • Place of Presentation: 米国シカゴ
  • Invited
• [Presentation] Molecular profiling of small cell lung cancers in Japanese patients (2013)
  • Author(s): Kazushige Wakuda
  • Organizer: 49th American Society of Clinical Oncology
  • Place of Presentation: 米国シカゴ
  • Invited
• [Presentation] Implementation of multiplexed mutational profiling into the lung cancer clinic at Shizuoka Cancer Center (2012)
  • Author(s): 芹澤昌邦
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Title: Biomarker analysis of lung cancer by Formalin-Fixed Paraffin-Embedded samples (2012)
  • Author(s): 剱持広知
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Title: Biomarker analysis of lung cancer by pleural or pericardial effusion samples (2012)
  • Author(s): 内藤立暁
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Title: Biomarker analysis of lung cancer by surgically resected samples (2012)
  • Author(s): 井坂光宏
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Multiplexed mutational profiling in Japanese patients with thoracic malignancies for personalized cancer therapy (2012)
  • Author(s): Masakuni Serizawa
  • Organizer: EORTC-NCI-AACR Symposium on 'Molecular Targets and Cancer Therapeutics'
  • Place of Presentation: ダブリン（アイルランド）
• [Book] 変化を厭わない (2014)
  • Author(s): 山本信之
  • Total Pages: 1
  • Publisher: 呼吸と循環
• [Book] 最新がん薬物療法学－がん薬物療法の最新知見 (2014)
  • Author(s): 赤松弘朗
  • Publisher: 中外医学社
• [Book] 肺癌診療Q&A第2版一つ上をいく診療の実践 (2013)
  • Author(s): 赤松弘朗
  • Publisher: 中外医学社