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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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2021: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | 長鎖シークエンサー / 肝癌 / 転写産物の全長 / HBV / 長鎖シークエンス / トランスクリプトーム / 長鎖シークエンス技術 / B型肝炎ウイルス / 転写産物 / 発現解析 |
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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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| 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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Report
(5 results)
Research Products
(22 results)
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[Journal Article] Classification of primary liver cancer with immunosuppression mechanisms and correlation with genomic alterations.2020
Author(s)
Fujita M, Yamaguchi R, Hasegawa T, Shimada S, Arihiro K, Hayashi S, Maejima K, Nakano K, Fujimoto A, Ono A, Aikata H, Ueno M, Hayami S, Tanaka H, Miyano S, Yamaue H, Chayama K, Kakimi K, Tanaka S, Imoto S, Nakagawa H.
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Journal Title
EBioMedicine
Volume: 53
Pages: 102659-102659
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comprehensive Analysis of Indels in Whole-genome Microsatellite Regions and Microsatellite Instability across 21 Cancer Types2020
Author(s)
Fujimoto A*, Fujita M, Hasegawa T, Wong JH, Maejima K, Oku-Sasaki A, Nakano K, Shiraishi Y, Miyano S, Yamamoto G, Akagi K, Imoto S, and Nakagawa H
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Journal Title
Genome Research
Volume: 30
Issue: 3
Pages: 334-34
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Whole genome sequencing and mutation rate analysis of trios with paternal dioxin exposure2018
Author(s)
Ton ND, Nakagawa H, Ha NH, Duong NT, Nhung VP, Hien LTT, Hue HTT, Hoang NH, Wong JH, Nakano K, Maejima K, Sasaki-Oku A, Tsunoda T, Fujimoto A*, Van Hai N.
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Journal Title
Hum Mutat.
Volume: 10
Issue: 10
Pages: 1384-1392
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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