A novel model of signal transduction according to transcripts

• Project/Area Number: 25293090
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• 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)
• Co-Investigator(Kenkyū-buntansha): SAKAO YUKINORI 愛知県がんセンター(研究所), 分子腫瘍学部, 研究員 (00274605) ; 樋田 豊明 愛知県がんセンター(研究所), 分子腫瘍学部, 研究員 (80250249)
• Co-Investigator(Renkei-kenkyūsha): HIDA TOYOAKI 愛知県がんセンター(研究所), 分子腫瘍学部, 研究員 (80250249)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 肺癌 / 分子病理学 / 腺癌 / EGFR / KRAS / 腫瘍進展 / 遺伝子変異 / 染色体破砕 / 肺癌発がんモデル / 肺腺癌 / 発がん機序 / 肺癌分類 / 腺扁平上皮癌 / HNF4α / 浸潤性粘液癌

Outline of Final Research Achievements

We focused on the following four themes in this study.
1) A novel model of signal transduction according to transcripts: We found HNF4a functioned as a master regulator for invasive mucinous adenocarcinoma. Also, a novel fusion involving NRG1 was identified in this subtype. 2) Non-stepwise model of lung adenocarcinoma development: We had some findings that supported no-stepwise progression using preinvasive lesions. 3) Genetic heterogeneity of cancer: We analyzed discordant results between protein expression and gene rearrangement of a driver gene for the lung, ALK. 4) Diagnostic application of molecular findings: We contributed to generate guidelines for molecular testing and formulation of basic data for primary-unknown cancers.

Research Products

• [Journal Article] Programmed Death-Ligand 1 Immunohistochemistry in Lung Cancer: In what state is this art? (2015)
  • Author(s): Kerr KM, Tsao MS, Nicholson AG, Yatabe Y, Wistuba, II, Hirsch FR, et al.
  • Journal Title: J Thorac Oncol. Volume: 10 Issue: 7 Pages: 985-9
  • DOI: 10.1097/jto.0000000000000526
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first or third generation TKIs. (2015)
  • Author(s): Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Park J, Kondo C, Shimoji M, Sato K, Suda K, Tomizawa K, Takemoto T, Hida T, Nishio K, and Mitsudomi T
  • Journal Title: Clinical Cancer Research Volume: 21 Issue: 23 Pages: 5305-5313
  • DOI: 10.1158/1078-0432.ccr-15-1046
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genetic features of pulmonary adenocarcinoma presenting with ground-glass nodules: the differences between nodules with and without growth. (2015)
  • Author(s): Kobayashi Y, Mitsudomi T, Sakao Y, Yatabe Y
  • Journal Title: Annals of Oncology Volume: 26 Issue: 1 Pages: 156-161
  • DOI: 10.1093/annonc/mdu505
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Comprehensive genomic profiles of small cell lung cancer. (2015)
  • Author(s): George, J., Lim, J. S., Jang, S. J., Cun, Y., Ozretic, L., Kong, G., . . . Yatabe, Y., Thomas, R. K.
  • Journal Title: Nature Volume: 524 Issue: 7563 Pages: 47-53
  • DOI: 10.1038/nature14664
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] EGFR mutation testing practices within the Asia Pacific region: Results of a multicenter diagnostic (2015)
  • Author(s): Yatabe, Y. Kerr, K. M. Utomo, A. Rajadurai, P. Tran, V. K. Du, X. Chou, T. Y. Enriquez, M. L. Lee, G. K. Iqbal, J. Shuangshoti, S. Chung, J. H. Hagiwara, K. Liang, Z. Normanno, N. Park, K. Toyooka, S. Tsai, C. M. Waring, P. Zhang, L. McCormack, R. Ratcliffe, M. Itoh, Y. Sugeno, M. Mok, T.
  • Journal Title: J Thorac Oncol Volume: 10 Issue: 3 Pages: 438-45
  • DOI: 10.1097/jto.0000000000000422
  • Peer Reviewed
• [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] The association between baseline clinical-radiological characteristics and growth of pulmonary nodules with ground-glass opacity. (2014)
  • Author(s): Kobayashi Y, Sakao Y, Deshpande GA, Fukui T, Mizuno T, Kuroda H, Sakakura N, Usami N, Yatabe Y, Mitsudomi T.
  • Journal Title: Lung Cancer. Volume: 83 Issue: 1 Pages: 61-66
  • DOI: 10.1016/j.lungcan.2013.10.017
  • Peer Reviewed
• [Journal Article] Era of comprehensive cancer genome analyses (2014)
  • Author(s): Yatabe, Y. Thomas, R. K.
  • Journal Title: J Clin Oncol Volume: 32 Issue: 36 Pages: 4029-30
  • DOI: 10.1200/jco.2014.58.4375
  • Peer Reviewed / Open Access
• [Journal Article] HNF4alpha as a marker for invasive mucinous adenocarcinoma of the lung. (2013)
  • Author(s): Sugano M, Nagasaka T, Sasaki E, Murakami Y, Hosoda W, Hida T, Mitsudomi T and Yatabe Y.
  • Journal Title: Am J Surg Pathol. Volume: 37 Issue: 2 Pages: 211-8
  • DOI: 10.1097/pas.0b013e31826be303
  • Peer Reviewed
• [Journal Article] EGFR mutation analysis in sputum of lung cancer patients: A multitechnique study. (2013)
  • Author(s): Hubers AJ, Heideman DA, Yatabe Y, Wood MD, Tull J, Taron M, Molina MA, Mayo C, Bertran-Alamillo J, Herder GJ, Koning R, Sie D, Ylstra B, Meijer GA, Snijders PJ, Witte BI, Postmus PE, Smit EF and Thunnissen E.
  • Journal Title: Lung Cancer Volume: 82 Issue: 1 Pages: 38-43
  • DOI: 10.1016/j.lungcan.2013.07.011
  • 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
• [Journal Article] Surgery for NSCLC in the era of personalized medicine (2013)
  • Author(s): Mitsudomi T, Suda K and Yatabe Y.
  • Journal Title: Nat Rev Clin Oncol. Volume: 10 Issue: 4 Pages: 235-44
  • DOI: 10.1038/nrclinonc.2013.22
  • Peer Reviewed
• [Journal Article] Diagnosis of lung adenocarcinoma in resected specimens: 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, Nakatani Y, Petersen I, Roggli V, Thunnissen E and Tsao M.
  • Journal Title: Arch Pathol Lab Med. Volume: 137 Issue: 5 Pages: 685-705
  • DOI: 10.5858/arpa.2012-0264-ra
  • Peer Reviewed
• [Journal Article] Interobserver agreement in the nuclear grading of primary pulmonary adenocarcinoma. (2013)
  • Author(s): Nakazato Y, Maeshima AM, Ishikawa Y, Yatabe Y, Fukuoka J, Yokose T, Tomita Y, Minami Y, Asamura H, Tachibana K, Goya T and Noguchi M.
  • Journal Title: J Thorac Oncol. Volume: 8 Issue: 6 Pages: 736-43
  • DOI: 10.1097/jto.0b013e318288dbd8
  • Peer Reviewed
• [Journal Article] Time to first cigarette and lung cancer risk in Japan. (2013)
  • Author(s): Ito H, Gallus S, Hosono S, Oze I, Fukumoto K, Yatabe Y, Hida T, Mitsudomi T, Negri E, Yokoi K, Tajima K, La Vecchia C, Tanaka H and Matsuo K.
  • Journal Title: Ann Oncol. Volume: 24 Issue: 11 Pages: 2870-2875
  • DOI: 10.1093/annonc/mdt362
  • Peer Reviewed
• [Presentation] 肺癌の分子生物学 (2015)
  • Author(s): 谷田部 恭
  • Organizer: 第56回日本肺癌学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-11-27
  • Invited
• [Presentation] 肺癌診療に必要な分子診断の基礎知識 (2015)
  • Author(s): 谷田部 恭
  • Organizer: 第56回日本肺癌学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-11-26
  • Invited
• [Presentation] 肺の新WHO分類（第4版）の要点. (2015)
  • Author(s): 谷田部恭
  • Organizer: 第54回日本臨床細胞学会秋期大会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-11-22
  • Invited
• [Presentation] 病理におけるコンパニオン診断ーOverview. (2015)
  • Author(s): 谷田部恭
  • Organizer: 第61回日本病理学会秋期特別総会
  • Place of Presentation: 東京大学安田講堂（東京都文京区）
  • Year and Date: 2015-11-06
  • Invited
• [Presentation] コンパニオン診断の問題点と展望 (2015)
  • Author(s): 谷田部 恭
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] 2015肺癌WHO分類における変更点 (2015)
  • Author(s): 谷田部恭
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] How do we use IHC in diagnostic pathology (2015)
  • Author(s): YATABE Y.
  • Organizer: IASLC Pathology Panel
  • 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 – 2015-03-21
  • Invited
• [Presentation] 臨床医のための分子病理診断の基礎 (2014)
  • Author(s): 谷田部 恭
  • Organizer: 日本肺癌学会
  • Place of Presentation: 国立京都国際会館 京都府
  • Year and Date: 2014-11-14 – 2014-11-16
  • Invited
• [Presentation] 肺腺癌を規定するベクトル (2014)
  • Author(s): 谷田部 恭
  • Organizer: 日本細胞診学会
  • Place of Presentation: パシフィコ横浜 神奈川県
  • Year and Date: 2014-06-06
  • Invited
• [Presentation] How do Experts manage difficult cases (2013)
  • Author(s): Yasushi Yatabe
  • Organizer: American Thoracic Society's international conference
  • Place of Presentation: Philadelphia, USA
  • Invited
• [Presentation] Radiological Characteristics of ALK-Positive Lung Cancer (2013)
  • Author(s): Yasushi Yatabe
  • Organizer: Annual meeting of Fleischner Society
  • Place of Presentation: Jeju, Korea
• [Presentation] Molecular diagnostics in Lung Cancer (2013)
  • Author(s): Yasushi Yatabe
  • Organizer: Pulmonary Pathology Society 2013 Biennial Meeting
  • Place of Presentation: Grenoble France
  • Invited
• [Presentation] Lung Cancer Pathology (2013)
  • Author(s): Yasushi Yatabe
  • Organizer: 69th Korea Congress of Radiology
  • Place of Presentation: Seoul, Korea
  • Invited
• [Presentation] AIS and the well differentiated spectrum (2013)
  • Author(s): Yasushi Yatabe
  • Organizer: 15th World Conference on Lung Cancer
  • Place of Presentation: Sydney, Australia
  • Invited
• [Book] WHO classification of tumours of the lung, pleura, thymus, and heart (2015)
  • Author(s): Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG
  • Total Pages: 412
  • Publisher: International Agency for Research on Cancer