Study for oncovirus-mediated epigenetic abnormality in the early phase of tumorigenesis
Project/Area Number |
18K08317
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | The University of Tokyo |
Principal Investigator |
Yamagishi Makoto 東京大学, 大学院新領域創成科学研究科, 特任講師 (90625261)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | HTLV-1 / EBV / エピジェネティクス / シングルセル解析 / ウイルス / エピゲノム / トランスクリプトーム / EBウイルス / 悪性リンパ腫 / EZH2 |
Outline of Final Research Achievements |
We performed integrative molecular analyses of over time samples from patients with ATL and asymptomatic HTLV-1 carriers (AC) to provide direct evidence of molecular time and disease progression and to identify the common epigenetic abnormalities. We found that the HTLV-1 infected cells from all infected individuals including patients with ATL and also AC with low proviral loads showed abnormal transcriptome with largely common pattern. ATAC-seq and ChIP-seq revealed that epigenetic dysregulation of infected cells is a background characteristic of the abnormal transcriptome. Importantly, disease-specific chromatin structure and histone modification pattern are involved in the progression of infected cells. The results provide the possible mechanism of virus-associated epigenetic abnormality that is a molecular basis of ATL development. Furthermore, we successfully identified some important functional genes involved in the pathogenesis of ATL.
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Academic Significance and Societal Importance of the Research Achievements |
前癌状態の解明は、癌の予防、早期治療介入を達成する上で不可欠である。HTLV-1及びEBV感染は最初のhitであることは自明であるが、発症リスク評価は確立されておらず、臨床的に有効な介入法もない。関連疾患発症後の予後は極めて不良である。本研究の成果は、将来の早期治療介入の実現において重要な基礎的データであり、今後のさらなる研究によってエピゲノム異常を標的としたより安全で効果の高い治療法の開発が促進されると期待される。また、エピゲノム異常による素地の形成が、がんの進化過程において不可欠であることを示す重要な成果である。
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Report
(4 results)
Research Products
(37 results)
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[Journal Article] A high-throughput detection method for the clonality of Human T-cell leukemia virus type-1-infected cells in vivo2020
Author(s)
Saito M, Hasegawa H, Yamauchi S, Nakagawa S, Sasaki D, Nao N, Tanio M, Wada Y, Matsudaira T, Momose H, Kuramitsu M, Yamagishi M, Nakashima M, Nakahata S, Iha H, Ogata M, Imaizumi Y, Uchimaru K, Morishita K, Watanabe T, Miyazaki Y, Yanagihara K.
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Journal Title
Int J Hematol.
Volume: 112
Issue: 3
Pages: 300-306
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mortality and risk of progression to adult T-cell leukemia/lymphoma in HTLV-1-associated myelopathy/tropical spastic paraparesis.2020
Author(s)
Nagasaka M, Yamagishi M, Yagishita N, Araya N, Kobayashi S, Makiyama J, Kubokawa M, Yamauchi J, Hasegawa D, Coler-Reilly ALG, Tsutsumi S, Uemura Y, Arai A, Takata A, Inoue E, Hasegawa Y, Watanabe T, Suzuki Y, Uchimaru K, Sato T, Yamano Y.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 117(21)
Issue: 21
Pages: 11685-11691
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Successful clinical sequencing by molecular tumor board in an elderly patient with refractory Sezary syndrome2020
Author(s)
Hijikata K, Yokoyama K (co-1st and co-corresponding author), Yokoyama N, Matsubara Y, Shimizu E, Nakashima M, Yamagishi M, Ota Y, Lim L, Yamaguchi R, Ito M, Tanaka Y, Denda T, Tani K, Yotsuyanagi H, Imoto S, Miyano S, Uchimaru K, Tojo A.
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Journal Title
JCO Precis Oncol
Volume: 4
Issue: 4
Pages: 534-560
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mortality and risk of progression to adult T-cell leukemia/lymphoma in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.2020
Author(s)
Nagasaka M, Yamagishi M, Yagishita N, Araya N, Kobayashi S, Makiyama J, Kubokawa M, Yamauchi J, Hasegawa D, Coler-Reilly A, Tsutsumi S, Uemura Y, Arai A, Takata A, Inoue E, Hasegawa Y, Watanabe T, Suzuki Y, Uchimaru K, Sato T, Yamano Y.
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Journal Title
Proc. Natl. Acad. Sci. U S A
Volume: in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Activation of PERK-ATF4-CHOP pathway as a novel therapeutic approach for efficient elimination of HTLV-1-infected cells.2020
Author(s)
Ikebe E, Matsuoka S, Tezuka K, Kuramitsu M, Okuma K, Nakashima M, Kobayashi S, Makiyama J, Yamagishi M, Oyadomari S, Uchimaru K, Hamaguchi I.
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Journal Title
Blood Adv
Volume: in press
Related Report
Peer Reviewed / Open Access
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[Journal Article] Targeting Excessive EZH1 and EZH2 Activities for Abnormal Histone Methylation and Transcription Network in Malignant Lymphomas2019
Author(s)
Yamagishi M., Hori M., Fujikawa D., Ohsugi T., Honma D., Adachi N., Katano H., Hishima T., Kobayashi S., Nakano K., Nakashima M., Iwanaga M., Utsunomiya A., Tanaka Y., Okada S., Tsukasaki K., Tobinai K., Araki K., Watanabe T., Uchimaru K.
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Journal Title
Cell Reports
Volume: 29
Issue: 8
Pages: 2321-2337
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CD4+ CADM1+ cell percentage predicts disease progression in HTLV-1 carriers and indolent adult T-cell leukemia/lymphoma.2019
Author(s)
Makiyama J, Kobayashi S, Watanabe E, Ishigaki T, Kawamata T, Nakashima M, Yamagishi M, Nakano K, Tojo A, Watanabe T, Uchimaru K.
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Journal Title
Cancer Sci.
Volume: 110(12)
Issue: 12
Pages: 3746-3753
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach2019
Author(s)
Katsuya H, Islam S, Tan, Ito J, Miyazato P, Matsuo, Inada Y, Iwase, Uchiyama Yoshikazu、Hata Hiroyuki、Sato T, Yagishita N, Araya N, Ueno T, Nosaka K, Tokunaga M, Yamagishi M, Watanabe T, Uchimaru K, Fujisawa J-i, Utsunomiya A, Yamano Y, Satou Y
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Journal Title
Cell Reports
Volume: 29
Issue: 3
Pages: 724-735
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Transcriptomic and epigenomic characteristics of HTLV-1-infected cells in asymptomatic carriers, HAM/TSP, and ATL2019
Author(s)
Makoto Yamagishi, Seiichiro Kobayashi, Junya Makiyama, Natsumi Araya, Makoto Nakashima, Masako Iwanaga, Atae Utsunomiya, Yuetu Tanaka, Toshiki Watanabe, Yoshihisa Yamano, Kaoru Uchimaru
Organizer
19th International Conference on Human Retrovirology HTLV and Related Viruses
Related Report
Int'l Joint Research
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