Exploration of the multi-step hepatocarcinogenesis based on the multi-omics strategy.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15964
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kyoto University
• Principal Investigator: Takeda Haruhiko 京都大学, 医学研究科, 特定病院助教 (40647525)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: ゲノム解析 / 肝発癌 / オミックス解析 / 全ゲノムシーケンス

Outline of Final Research Achievements

Liver cancer is one of the most lethal malignancies, and genome-based personalized therapy is highly expected. In this study, we aimed to examine the candidates of the genetic alterations characteristic to each step of multistage hepatocarcinogenesis, especially in the early step of cancer development. We conducted multiregional sampling from the premalignant small liver nodules surgically resected along with the classical hepatocellular carcinomas and examined their characteristics through the multi-omics strategy especially with the whole-genome sequencing. We detected various genetic alterations, not only single nucleotide variants but also chromosomal translocations, even in the premalignant liver nodules or early small hepatocellular carcinomas which might be out of the targets of treatment in the clinical practice to date. Phylogenetical analysis demonstrated the mutational patterns differed between the early and progressive phases of the multistage hepatocarcinogenesis.

Free Research Field

肝癌

Academic Significance and Societal Importance of the Research Achievements

本研究では一般的に治療対象前と考えられる早期の肝内結節および治療対象の肝細胞癌のゲノム異常を比較検討することで、初期および進行期に獲得されるゲノム異常を全ゲノムシーケンス解析にて明らかにした。多段階肝発癌の初期および進行期の遺伝子異常について全ゲノムレベルで解析することで、多段階肝発癌メカニズムの解明に寄与するとともに、ゲノム進化過程に基づいた分子標的治療の最適化につなげる基礎的知見を得たことから、将来的なゲノム医療の発展に寄与するものと考えられる。