Genomic profiling of large-cell neuroendocrine cartinoma of the lung for the development of new targeted therapies

• Project/Area Number: 26870876
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology; Tumor therapeutics
• Research Institution: National Cancer Center Japan
• Principal Investigator: Umemura Shigeki 国立研究開発法人国立がん研究センター, 東病院呼吸器内科, 医員 (80623967)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 分子標的薬 / 癌遺伝子 / 大細胞神経内分泌癌 / 分子標的治療 / がん遺伝子 / 大細胞神経内分泌肺癌

Outline of Final Research Achievements

Little is known about the molecular features of large-cell neuroendocrine carcinoma of the lung (LCNEC). We performed targeted capture sequencing of 78 LCNEC samples (65 surgically resected cases and 13 advanced cases) and obtained the overview of the biologically relevant genetic alterations of LCNEC. We found a relatively high prevalence of inactivating mutations in TP53 and RB1 in the same way as SCLC. Genetic alterations in the PI3K/AKT/mTOR pathway were detected in 13 (17%) of the tumors and other well-known activating alterations were detected in EGFR (1 case, 1%) and ERBB2 (1 case, 1%). LCNEC had a similar genomic profile to SCLC, including promising therapeutic targets such as the PI3K/AKT/mTOR pathway and other well-known gene alterations.

Research Products

• [Presentation] 次世代シークエンサーを用いた大細胞神経内分泌肺癌の遺伝子プロファイリング (2015)
  • Author(s): 三好智裕 梅村茂樹 松村勇輝 三牧幸代 多田智史 石井源一郎 松本慎吾 葉清隆 仁保誠治 大松広伸 青景圭樹 菱田智之 吉田純司 永井完治 後藤功一 坪井正博 土原一哉
  • Organizer: 日本肺癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2015-11-28
• [Presentation] Genomic profiling of large-cell neuroendocrine carcinoma of the lung. (2015)
  • Author(s): Miyoshi T, Umemura S, Matsumura Y, Mimaki S, Tada S, Ishii G, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Aokage K, Hishida T, Yoshida J, Nagai K, Goto K, Tsuboi M, Tsuchihara K
  • Organizer: ASCO
  • Place of Presentation: アメリカ、シカゴ
  • Year and Date: 2015-06-01
  • Int'l Joint Research