Difference in mutation distribution between adenocarcinoma in situ and early lung adenocarcinoma

• Project/Area Number: 16KT0197
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: National Cancer Center Japan
• Principal Investigator: Shiraishi Kouya 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (80609719)
• Project Period (FY): 2016-07-19 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 非浸潤性肺腺がん / 浸潤性肺腺がん / 遺伝子異常 / 早期肺がん / 同時多発がん / ゲノム解析 / 前がん病変 / 次世代シークエンス / 早期発見 / 肺がん

Outline of Final Research Achievements

We performed the targeted sequencing of 10 pair samples, including non-invasive (adenocarcinoma in situ) and invasive lung adenocarcinoma tissue from never-smoking female, using the Ion AmpliSeqTM Cancer Hotspot Panel v2. As results of sequencing, in three of ten patients, EGFR and TP53 mutations were detected in both adenocarcinoma in situ and invasive lung adenocarcinoma, however, driver mutations including EGFR mutations were only detected in adenocarcinoma in situ. These results were similar to previous reported of lung cancer in Caucasian.

Academic Significance and Societal Importance of the Research Achievements

本研究は、今まで行われてこなかった同時多発を来たした症例由来の非浸潤性肺腺がんと浸潤性肺腺がんに対するゲノム解析を行うことで、がんの進展過程に関わる遺伝子異常の同定やメカニズムの解明、さらには新しい治療標的の探索を試みた。本研究により、既報で報告があったようにTP53遺伝子異常ががんの進展において重要な役割を果たしている可能性が示された。しかし本研究では、解析対象数が少ないために、再現性のある遺伝子異常や新規治療標的因子の同定には至らなかった。今後は症例数を増やして解析することで、本結果が再現されるか検証する予定である。

Research Products

• [Journal Article] Radiopathologic correlation of collision lung cancer with ground-glass opacity (2018)
  • Author(s): Uchida Shinsuke、Tsuta Koji、Kusumoto Masahiko、Shiraishi Kouya、Kohno Takashi、Watanabe Shun-ichi
  • Journal Title: Asian Cardiovascular and Thoracic Annals Volume: 27 Issue: 1 Pages: 45-48
  • DOI: 10.1177/0218492318811549
  • Peer Reviewed
• [Journal Article] Common TDP1 Polymorphisms in Relation to Survival among Small Cell Lung Cancer Patients: A Multicenter Study from the International Lung Cancer Consortium. (2017)
  • Author(s): Lohavanichbutr P, Sakoda LC, Amos CI, Arnold SM, Christiani DC, Davies MPA, Field JK, Haura EB, Hung RJ, Kohno T, Landi MT, Liu G, Liu Y, Marcus MW, O'Kane GM, Schabath MB, Shiraishi K, Slone SA, Yang P, Yoshida K, Zhang R, Zong X, Goodman GE, Weiss NS, Chen C.
  • Journal Title: Clin Cancer Res. Volume: 23 Issue: 24 Pages: 7550-7557
  • DOI: 10.1158/1078-0432.ccr-17-1401
  • Peer Reviewed / Int'l Joint Research