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Intratumoral heterogeneity and clonal evolution in liver cancer

Author

Listed:
  • Bojan Losic

    (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Amanda J. Craig

    (Icahn School of Medicine at Mount Sinai)

  • Carlos Villacorta-Martin

    (Icahn School of Medicine at Mount Sinai)

  • Sebastiao N. Martins-Filho

    (Icahn School of Medicine at Mount Sinai
    University of Sao Paulo School of Medicine)

  • Nicholas Akers

    (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
    Adaptive Biotechnologies)

  • Xintong Chen

    (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai)

  • Mehmet E. Ahsen

    (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai)

  • Johann Felden

    (Icahn School of Medicine at Mount Sinai
    University Medical Center Hamburg-Eppendorf)

  • Ismail Labgaa

    (Icahn School of Medicine at Mount Sinai
    Lausanne University Hospital CHUV)

  • Delia DʹAvola

    (Icahn School of Medicine at Mount Sinai
    Clínica Universidad de Navarra)

  • Kimaada Allette

    (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Sergio A. Lira

    (Icahn School of Medicine at Mount Sinai)

  • Glaucia C. Furtado

    (Icahn School of Medicine at Mount Sinai)

  • Teresa Garcia-Lezana

    (Icahn School of Medicine at Mount Sinai)

  • Paula Restrepo

    (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai)

  • Ashley Stueck

    (Dalhousie University)

  • Stephen C. Ward

    (Icahn School of Medicine at Mount Sinai)

  • Maria I. Fiel

    (Icahn School of Medicine at Mount Sinai)

  • Spiros P. Hiotis

    (Icahn School of Medicine at Mount Sinai)

  • Ganesh Gunasekaran

    (Icahn School of Medicine at Mount Sinai)

  • Daniela Sia

    (Icahn School of Medicine at Mount Sinai)

  • Eric E. Schadt

    (Icahn School of Medicine at Mount Sinai
    Sema4, a Mount Sinai venture)

  • Robert Sebra

    (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Sema4, a Mount Sinai venture)

  • Myron Schwartz

    (Icahn School of Medicine at Mount Sinai)

  • Josep M. Llovet

    (Icahn School of Medicine at Mount Sinai
    Hospital Clinic, Universitat de Barcelona
    Institució Catalana de Recerca i Estudis Avançats)

  • Swan Thung

    (Icahn School of Medicine at Mount Sinai)

  • Gustavo Stolovitzky

    (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
    IBM T. J. Watson Research Center, Yorktown Heights)

  • Augusto Villanueva

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

Abstract

Clonal evolution of a tumor ecosystem depends on different selection pressures that are principally immune and treatment mediated. We integrate RNA-seq, DNA sequencing, TCR-seq and SNP array data across multiple regions of liver cancer specimens to map spatio-temporal interactions between cancer and immune cells. We investigate how these interactions reflect intra-tumor heterogeneity (ITH) by correlating regional neo-epitope and viral antigen burden with the regional adaptive immune response. Regional expression of passenger mutations dominantly recruits adaptive responses as opposed to hepatitis B virus and cancer-testis antigens. We detect different clonal expansion of the adaptive immune system in distant regions of the same tumor. An ITH-based gene signature improves single-biopsy patient survival predictions and an expression survey of 38,553 single cells across 7 regions of 2 patients further reveals heterogeneity in liver cancer. These data quantify transcriptomic ITH and how the different components of the HCC ecosystem interact during cancer evolution.

Suggested Citation

  • Bojan Losic & Amanda J. Craig & Carlos Villacorta-Martin & Sebastiao N. Martins-Filho & Nicholas Akers & Xintong Chen & Mehmet E. Ahsen & Johann Felden & Ismail Labgaa & Delia DʹAvola & Kimaada Allett, 2020. "Intratumoral heterogeneity and clonal evolution in liver cancer," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14050-z
    DOI: 10.1038/s41467-019-14050-z
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    Cited by:

    1. Zhenzhen Chen & Qiankun He & Tiankun Lu & Jiayi Wu & Gaoli Shi & Luyun He & Hong Zong & Benyu Liu & Pingping Zhu, 2023. "mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Bing He & Yao Xiao & Haodong Liang & Qianhui Huang & Yuheng Du & Yijun Li & David Garmire & Duxin Sun & Lana X. Garmire, 2023. "ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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