2021 Fiscal Year Final Research Report
Comprehensive analysis of full-length transcripts reveal novel splicing abnormalities and oncogenic transcripts in liver cancer
| Project/Area Number |
18H02680
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | The University of Tokyo (2019-2021)
Kyoto University (2018) |
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Principal Investigator |
Fujimoto Akihiro 東京大学, 大学院医学系研究科(医学部), 教授 (30525853)
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| Co-Investigator(Kenkyū-buntansha) |
中川 英刀 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (50361621)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | 長鎖シークエンサー / 肝癌 / 転写産物の全長 / HBV |
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| Outline of Final Research Achievements |
In this study, we developed an analysis pipeline named SPLICE and analyzed cDNA sequences from 42 pairs of hepatocellular carcinoma (HCC) and matched non-cancerous liver with Oxford Nanopore sequencer. Our analysis detected 46,663 transcripts from the protein-coding genes in the HCCs and the matched non-cancerous livers, of which 5,366 (11.5 %) were novel. Comparison of expression levels identified 9,933 differentially expressed transcripts (DETs) in 4,744 genes. Interestingly, 746 genes with DETs, including LINE1-MET transcript, were not found by the gene-level analysis. We also found that fusion transcripts of transposable elements and hepatitis B virus (HBV) were overexpressed in HCCs. In vitro experiments on DETs showed that LINE1-MET and HBV-human transposable elements promoted cell growth. Furthermore, fusion gene detection showed novel recurrent fusion events, which have not been detected short-reads.
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| Free Research Field |
人類遺伝学
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| Academic Significance and Societal Importance of the Research Achievements |
肝癌は、世界の癌死の第３位に挙げられる予後不良の癌であり、有効な治療法の確立が急務である。これらの疾患の発症機序解明や治療ターゲットの発見のために、多くのゲノム、転写産物の研究が行われてきた。しかし、それらの先行研究は、短鎖（リード長が短い）の次世代シークエンサー（NGS）を用いて行われており、リピートを介した構造異常の検出や、転写産物の全長の解析が不可能であった。本研究は、長鎖シークエンサーを用いた初の肝癌のトランスクリプトーム研究であり、発癌に寄与する遺伝子候補が多数同定された。
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