The genomic and epigenomic landscape in thymic carcinoma

• Project/Area Number: 26461206
• 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: National Cancer Center Japan
• Principal Investigator: Fujiwara Yutaka 国立研究開発法人国立がん研究センター, 中央病院, 医長 (70464261)
• Research Collaborator: Asao Tetsuhiko ; Kohno Takashi ; Ichikawa Hitoshi ; Saito Motonobu
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 胸腺癌 / 化学療法 / 遺伝子Profile / 次世代シークエンサー / thymic carcinoma / TET2 / DNA methylation / 胸腺がん / がん遺伝子 / 遺伝子増幅 / 遺伝子変異 / 遺伝子癒合 / 遺伝子融合

Outline of Final Research Achievements

The aim of this study is to investigate the genomic and epigenomic alterations by next generation sequencing of thymic cancer as target for anti-cancer therapy. Sixty-four consecutive patients with thymic carcinoma treatedat the National Cancer Hospital between 1973 and 2014 were included in this study.
Tissue samples of 52 patients (81.3%) were available for targeted sequencing of mutation hot spots in 50cancer-related genes by IonAmpliseq Cancer Hotspot Panel v2. The genetic alterations of TP53, KRAS, FBXW7, and NRAS were detected in 7 patients (13.5%).　In whole exome and transcriptome sequencing from paired snap-frozen cancerous or non-cancerous tissues (n=10), we identified a mutation signature consisting of enrichment for C>T substitutions at CpG dinucleotides. And we also identifies thymic cancers with TET2 mutations had more hypermethylated genes than those without, and hyper-methylation was associated with downregulation of gene expression.

Research Products

• [Journal Article] Medical treatment involving investigational drugs and genetic profile of thymic carcinoma. (2016)
  • Author(s): Asao T, Fujiwara Y, Sunami K, Kitahara S, Goto Y, Kanda S, Horinouchi H, Nokihara H, Yamamoto N, Ichikawa H, Kohno T, Tsuta K, Watanabe S, Takahashi K, Ohe Y.
  • Journal Title: Lung Cancer Volume: 93 Pages: 77-81
  • DOI: 10.1016/j.lungcan.2016.01.004
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Retrospective analysis of 64 consecutive patients with thymic cancer (2015)
  • Author(s): Tetsuhiko Asao, Yutaka Fujiwara, Kuniko Sunami, Shinsuke Kitahara, Shintaro Kanda, Hidehito Horinouchi, Hiroshi Nokihara, Noboru Yamamoto, Reika Iwakawa-Kawabata, Takashi Kohno, Koji Tsuta, Shun-ichi Watanabe, Hisao Asanuma, and Yuichiro Ohe
  • Organizer: 第112回日本内科学会
  • Place of Presentation: 京都
  • Year and Date: 2015-04-10