Establishment of a cancer diagnosis method using DNA increase derived from plasma tumor after the radiation therapy

• Project/Area Number: 16K19856
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: National Cancer Center Japan
• Principal Investigator: Kageyama Shun-ichiro 国立研究開発法人国立がん研究センター, 東病院, 医員 (60644979)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: cell free DNA / radiation / EGFR / digital PCR / sequence / 放射線治療 / エクソームシークエンス

Outline of Final Research Achievements

We investigated the plasma levels of tumor-specific cell-free DNA (cfDNA) in 17 stage I-II (early) and IV (advanced) non-small cell lung cancer (NSCLC) patients who underwent radiotherapy. Digital polymerase chain reaction (PCR) and targeted sequencing showed that total and tumor-specific cfDNA levels increased in response to radiotherapy in both early- and advanced-stage NSCLC patients. We detected high copy numbers of epidermal growth factor receptor mutations (L858R and T790M) in the cfDNA samples from stage IV NSCLC patients who underwent stereotactic body radiation therapy to treat brain metastasis related to tyrosine kinase inhibitor (TKI) treatment failure. In conclusion, our study demonstrates that radiotherapy increases tumoral cfDNA levels in the plasma and shows potential to serve as an indicator for diagnosing drug-resistant tumor-related gene mutations in early-stage NSCLC patients or those undergoing molecular targeted therapy.

Research Products

• [Journal Article] Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients. (2018)
  • Author(s): Kageyama S, Nihei K, Karasawa K,, Sawada T, Koizumi F, Yamaguchi S, Kato S, Hojo H, Motegi A, Tsuchihara K, Akimoto T.
  • Journal Title: Oncotarget Volume: 10;9(27) Issue: 27 Pages: 19368-19378
  • DOI: 10.18632/oncotarget.25053
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 放射線治療によるcell free DNA増加を利用した診断法の確立 (2017)
  • Author(s): 影山俊一郎
  • Organizer: 第18回放射線増感研究会
  • Place of Presentation: 奈良県文化会館（奈良県奈良市）
  • Year and Date: 2017-02-05
  • Invited
• [Presentation] 放射線治療後の血漿中腫瘍由来ＤＮＡを利用したシークエンス解析法の確立 (2017)
  • Author(s): 影山俊一郎
  • Organizer: 第３０回日本放射線腫瘍学会