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Multi-omics analysis for hepato-biliary-pancreatic cancers

Research Project

Project/Area Number 18H04049
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Nakagawa Hidewaki  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)

Co-Investigator(Kenkyū-buntansha) 井元 清哉  東京大学, 医科学研究所, 教授 (10345027)
山上 裕機  和歌山県立医科大学, 医学部, 教授 (20191190)
相方 浩  広島大学, 医系科学研究科(医), 准教授 (30403512)
中村 透  北海道大学, 医学研究院, 助教 (70645796)
二階堂 愛  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (00383290)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000)
Fiscal Year 2020: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2019: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2018: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Keywords肝胆膵がん / ゲノム / オミックス解析 / 分子分類 / 分子標的治療 / 腫瘍免疫 / 免疫 / RNA / プロテオーム / ゲノム解析 / 多層オミックス / がんゲノム
Outline of Final Research Achievements

For liver cancer, we performed immune-genomic analysis and classified it into four subgroups in the aspects of immune suppression mechanism. Proteome analysis classified liver cancers in the aspects of drug therapies. We clarified the cellular plasticity mechanism of combined types of liver cancer with HCC and cholangiocarcinoma. For cholagiocarcinoma, we identified drugs which can be applicable in each patient by using genomic and transcriptomic data. For pancreatic cancer, we performed genomic and transcriptomic analysis with microbiome analysis on small intestine and examined any effect of chemotherapy on pancreatic cancer immunology and microbiome.

Academic Significance and Societal Importance of the Research Achievements

本研究は、最も難治性である肝胆膵がんに照準をしぼり、そのゲノム、RNA,たんぱく質、免疫、腸内細菌叢といった多元的なオミックス解析を行い、肝胆膵がんの分子分類を確立し、また、個別化治療の提案をおこなうものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (44 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (9 results) Journal Article (22 results) (of which Int'l Joint Research: 16 results,  Peer Reviewed: 22 results,  Open Access: 21 results) Presentation (13 results) (of which Int'l Joint Research: 8 results,  Invited: 12 results)

  • [Int'l Joint Research] Samsung Medical Center(韓国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Broad Institute/MD Anderson Cancer Center/NCI(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Sanger Institute/Cambridge University/Cancer Res UK(英国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] 北京大学/BGI(中国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ソウル大学/サムソン病院/KAIST(韓国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ベローナ大学(イタリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] 北京大学(中国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] MDアンダーソンがんセンター(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Whole genome sequencing with long-reads reveals complex structure and origin of structural variation in human genetic variations and somatic mutations in cancer.2021

    • Author(s)
      Fujimoto A, Wong JH, Yoshii Y, Akiyama S, Tanaka A, Yagi H, Shigemizu D, Nakagawa H, Mizokami M, and Shimada M.
    • Journal Title

      Genome Medicine

      Volume: 13 Issue: 1 Pages: 65-65

    • DOI

      10.1186/s13073-021-00883-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor fibroblast growth factor receptor 4 level predicts the efficacy of Lenvatinib in patients with advanced hepatocellular carcinoma.2020

    • Author(s)
      Yamauchi M, Ono A, Ishikawa A, Kodama K, Uchikawa S, Hatooka H, Zhang P, Teraoka Y, Morio K, Fujino H, Nakahara T, Murakami E, Miki D, Kawaoka T, Tsuge M, Hiramatsu A, Imanura M, Hayes CN, Fujita M, Nakagawa H, Yusui W, Aikata H, and Chayama K.
    • Journal Title

      Clin Transl Gastroenterology

      Volume: 11 Issue: 5 Pages: e00179-e00179

    • DOI

      10.14309/ctg.0000000000000179

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neoantimon: A multifunctional R package for identification of tumor-specific neoantigens.2020

    • Author(s)
      Hasegawa T, Hayashi S, Nakagawa H, Miyano S, and Imoto S.
    • Journal Title

      Bioinformatics

      Volume: 36 Issue: 18 Pages: 4813-4816

    • DOI

      10.1093/bioinformatics/btaa616

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic characterization of pancreatic cancer patients and prediction of carrier status of germline pathogenic variants in cancer-predisposing genes2020

    • Author(s)
      Mizukami Keijiro、Iwasaki Yusuke、Kawakami Eiryo、Hirata Makoto、Kamatani Yoichiro、Matsuda Koichi、Endo Mikiko、Sugano Kokichi、Yoshida Teruhiko、Murakami Yoshinori、Nakagawa Hidewaki、Spurdle Amanda B.、Momozawa Yukihide
    • Journal Title

      EBioMedicine

      Volume: 60 Pages: 103033-103033

    • DOI

      10.1016/j.ebiom.2020.103033

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Organoid Biobank of Neuroendocrine Neoplasms Enables Genotype-Phenotype Mapping2020

    • Author(s)
      Kawasaki K、Toshimitsu K、Matano M、Fujita M、Kudo Atsushi、Kitagawa Y、Kanai T、Nakagawa H、Sato T, et.al.
    • Journal Title

      Cell

      Volume: 183 Issue: 5 Pages: 1420-1435

    • DOI

      10.1016/j.cell.2020.10.023

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genomic and transcriptomic landscape of gallbladder cancer for molecular classification and tumor microenvironment characterization.2020

    • Author(s)
      Ebata N, Fujita M, Sasagawa S, Maejima K, Okawa Y, Hatanaka Y, Mitsuhashi T, Oosawa A, Tanaka H, Miyano S, Nakamura T, Hirano S, and Nakagawa H
    • Journal Title

      Cancers

      Volume: 13 Issue: 4 Pages: 733-733

    • DOI

      10.3390/cancers13040733

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pan-cancer analysis of whole genomes2020

    • Author(s)
      The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
    • Journal Title

      Nature

      Volume: 578 Issue: 7793 Pages: 82-93

    • DOI

      10.1038/s41586-020-1969-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analyses of non-coding somatic drivers in 2,658 cancer whole genomes2020

    • Author(s)
      PCAWG Consortium
    • Journal Title

      Nature

      Volume: 578(7793) Issue: 7793 Pages: 102-111

    • DOI

      10.1038/s41586-020-1965-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Patterns of somatic structural variation in human cancer genomes.2020

    • Author(s)
      Li Y, Roberts ND, Wala JA, Shapira O, Schumacher SE, Kumar K, Khurana E, Waszak S, Korbel JO, Haber JE, Imielinski M; PCAWG Structural Variation Working Group, Weischenfeldt J, Beroukhim R, Campbell PJ; PCAWG Consortium.
    • Journal Title

      Nature

      Volume: 578 Pages: 112-121

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Repertoire of Mutational Signatures in Human Cancer.2020

    • Author(s)
      Alexandrov LB, Kim J, Haradhvala NJ, Huang MN, Ng AWT, Wu Y, Boot A, Covington KR, Gordenin DA, Bergstrom EN, Islam SM, Lopez-Bigas N, Klimczak LJ, McPherson JR, Morganella S, Sabarinathan R, Wheeler DA, Mustonen V, the PCAWG Mutational Signatures Working Group, Getz G, Rozen SG. & Stratton MR.
    • Journal Title

      Nature

      Volume: 578 Pages: 94-101

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The landscape of viral associations in human cancers.2020

    • Author(s)
      Zapatka M, Borozan I, Brewer DS, Iskar M, Grundhoff A, Alawi M, Desai N, Sültmann H, Moch H, PCAWG Pathogens Working Group, ICGC/TCGA Pan-cancer Analysis of Whole Genomes Network, Cooper CS, Eils R, Ferretti V, Peter Lichter P.
    • Journal Title

      Nature Genetics

      Volume: 52 Issue: 3 Pages: 320-330

    • DOI

      10.1038/s41588-019-0558-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive molecular characterization of mitochondrial genomes in human cancers.2020

    • Author(s)
      Yuan Y, Ju YS, Kim Y, Li J, Wang Y, Yang Y, Martincorena I, Creighton CJ, Weinstein JN, Xu Y, Kim H, Nakagawa H, Park K, Campbell PJ, Liang H, on behalf of the PCAWG Mitochondrial Genome Working Group and The PCAWG Network.
    • Journal Title

      Nature Genetics

      Volume: 52 Issue: 3 Pages: 342-352

    • DOI

      10.1038/s41588-019-0557-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.2020

    • Author(s)
      Zhang Y, Chen F, Fonseca NA, He Y, Fujita M, Nakagawa H, Zhang Z, Brazma A, Creighton CJ, on behalf of the PCAWG Transcriptome Working Group, PCAWG Structural Variation Working Group, PCAWG Network
    • Journal Title

      Nature Commun

      Volume: 11 Issue: 1 Pages: 736-736

    • DOI

      10.1038/s41467-019-13885-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      EBioMedicine

      Volume: 53 Pages: 102659-102659

    • DOI

      10.1016/j.ebiom.2020.102659

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Somatic mutation landscape reveals differential variability of cell-of-origin for primary liver cancer.2020

    • Author(s)
      Ha KH, Fujita M, Karkic R, Yang S, Xue R, Zhang C, Bai F, Zhang N, Hoshida Y, Polak P, Nakagawa H, Kim HG, and Lee HJ
    • Journal Title

      Heliyon

      Volume: 6 Issue: 2 Pages: e03350-e03350

    • DOI

      10.1016/j.heliyon.2020.e03350

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.2020

    • Author(s)
      Rodriguez-Martin B, Alvarez EG, Baez-Ortega A, PCAWG et al
    • Journal Title

      Nature Genet

      Volume: 52 Issue: 3 Pages: 306-319

    • DOI

      10.1038/s41588-019-0562-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Butler enables rapid cloud-based analysis of thousands of human genomes.2020

    • Author(s)
      Yakneen S, Waszak SM, PCAWG Technical Working Group, Gertz M & Korbel JO.
    • Journal Title

      Nature Biotechnol.

      Volume: 38 Issue: 3 Pages: 288-292

    • DOI

      10.1038/s41587-019-0360-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing2020

    • Author(s)
      PCAWG Consortium
    • Journal Title

      Nat Genet.

      Volume: 52(3) Issue: 3 Pages: 331-341

    • DOI

      10.1038/s41588-019-0576-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      Genome Research

      Volume: 30 Issue: 3 Pages: 334-34

    • DOI

      10.1101/gr.255026.119

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantifying immune-based counterselection of somatic mutations.2019

    • Author(s)
      Yang F, Kim DK, Nakagawa H, Hayashi S, Imoto S, Stein L, and Roth F
    • Journal Title

      PLoS Genet

      Volume: 15 Issue: 7 Pages: e1008227-e1008227

    • DOI

      10.1371/journal.pgen.1008227

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genomic analysis of pancreatic juice DNA assesses malignant risk of intraductal papillary mucinous neoplasm of pancreas2019

    • Author(s)
      Mateos Raul N.、Nakagawa Hidewaki、Hirono Seiko、...、Fujita Masashi
    • Journal Title

      Cancer Medicine

      Volume: 8 Issue: 10 Pages: 4565-4573

    • DOI

      10.1002/cam4.2340

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes2019

    • Author(s)
      Xue Ruidong、Chen Lu、Zhang Chong、Fujita Masashi et al.
    • Journal Title

      Cancer Cell

      Volume: 35 Issue: 6 Pages: 932-947

    • DOI

      10.1016/j.ccell.2019.04.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Whole Genome and Immuno-genomic Analysis of Liver Cancer2020

    • Author(s)
      Hidewaki Nakagawa
    • Organizer
      日本がん学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Immunogenomic analysis of liver cancer2020

    • Author(s)
      Masashi Fujita, Hidewaki Nakagawa
    • Organizer
      日本がん学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Genomic and transcriptomic landscape reveals molecular classification in gallbladder cancer2020

    • Author(s)
      Nobutaka Ebata, Hidewaki Nakagawa
    • Organizer
      日本がん学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Whole Genome and Immuno-genome Landscape of Liver Cancer2019

    • Author(s)
      Nakagawa H
    • Organizer
      The Asian Pacific Association for the study of the liver (APASL) meeting, Tokyo
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Whole genome and immuno-genomic analysis of liver cancer2019

    • Author(s)
      Nakagawa H and Fujita M
    • Organizer
      The 9th Asan Liver Center Symposium, Seoul, Korea
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Whole-Genome mutational landscape and characterization of non-coding and structural mutations in liver cancer2019

    • Author(s)
      Nakagawa H
    • Organizer
      Gordon Research Conference, Hong Kong, China
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] GEM Japan Updates2019

    • Author(s)
      Nakagawa H
    • Organizer
      GA4GH 7th Plenary National Initiatives Workshop
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 胆道がんの網羅的ゲノム解析からゲノム医療へ2019

    • Author(s)
      中川英刀、江畑信孝、平野聡
    • Organizer
      第55回日本胆道学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Whole genome and phosphor-proteomic analysis for liver cancers2018

    • Author(s)
      Nakagawa H
    • Organizer
      The 8th RPPA Global Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Whole genome sequencing and immuno-genomic analysis for liver cancer2018

    • Author(s)
      Nakagawa H
    • Organizer
      The 49th Princess Takamatsu Cancer Research Fund International Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Pan-cancer Whole Genome Sequencing Project (PCAWG) in ICGC/TCGA2018

    • Author(s)
      Nakagawa H
    • Organizer
      The 77th Annual Meeting of Japanese Cancer Association
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cancer Whole Genome Sequencing and Immuno-genomic Analysis for Cancer2018

    • Author(s)
      Nakagawa H
    • Organizer
      The 27th Korean Genome Organization Annual Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cancer Whole Genome Sequencing and Immuno-genomic Analysis for Cancer2018

    • Author(s)
      Nakagawa H
    • Organizer
      KAIST Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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