Whole genome sequencing analysis of multiple liver cancer nodules for determination of causal events for multi-occurrence

• Project/Area Number: 15K19915
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Furuta Mayuko 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (00647183)
• Research Collaborator: Nakagawa Hidewaki 国立研究開発法人理化学研究所, 統合生命医科学研究センター, チームリーダー (50361621) ; Fujimoto Akihiro 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 副チームリーダー (30525853)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 肝がん / 多発性 / 再発性 / 全ゲノムシークエンス / 肝臓がん / 多中心性腫瘍 / 転移性腫瘍 / ゲノム変異

Outline of Final Research Achievements

In this study, we performed whole genome and RNA sequencing analyses of 49 tumors including two extra-hepatic metastases, and one nodule-in-nodule tumor from 23 HCC patients for the discrimination between multi-centric (MC) and intrahepatic metastasis (IM). Sequencing-based molecular diagnosis using somatic single nucleotide variation information showed higher sensitivity compared to previous techniques and proved useful in cases, which showed inconsistent clinical diagnoses. In addition, whole genome sequencing offered advantages in profiling of other genetic alterations, such as structural variations, copy number alterations, and variant allele frequencies, and helped to confirm the IM/MC diagnosis. Divergent alterations between IM tumors with sorafenib treatment, long time-intervals, or tumor-in-tumor nodules indicated high intra-tumor heterogeneity, evolution, and clonal switching of liver cancers.

Research Products

• [Journal Article] Whole genome sequencing discriminates hepatocellular carcinoma with intrahepatic metastasis from multi-centric tumors (2017)
  • Author(s): Furuta M, Ueno M, Fujimoto A, Hayami S, Yasukawa S, Kojima F, Arihiro K, Kawakami Y, Wardell CP, Shiraishi Y, Tanaka H, Nakano K, Maejima K, Sasaki-Oku A, Tokunaga N, Boroevich KA, Abe T, Aikata H, Ohdan H, Gotoh K, Kubo M, Tsunoda T, Miyano S, Chayama K, Yamaue H, Nakagawa H
  • Journal Title: J Hepatol Volume: 66(2) Issue: 2 Pages: 363-373
  • DOI: 10.1016/j.jhep.2016.09.021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 多発性肝臓がんの全ゲノム解析による多発性がん発生と進化の分子機構の解明 (2015)
  • Author(s): 古田 繭子
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋）
  • Year and Date: 2015-10-08
• [Presentation] Whole genome sequencing analysis of multiple liver cancer nodules for determination of causal events for multi-occurrence (2015)
  • Author(s): Mayuko Furuta
  • Organizer: Ametican Association for Cancer Research
  • Place of Presentation: Philadelphia (USA)
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Remarks] 再発性と多発性肝臓がんのゲノム診断（理化学研究所）
  • URL: http://www.riken.jp/pr/press/2016/20161124_1/