Intratumoral heterogeneity and clonal evolution in liver cancer.

Carcinoma, Hepatocellular / genetics Clonal Evolution DNA Copy Number Variations Epitopes / genetics Gene Expression Regulation, Neoplastic Gene Regulatory Networks Genetic Heterogeneity Hepatitis B Antigens / genetics Hepatitis B virus / genetics High-Throughput Nucleotide Sequencing Humans Kaplan-Meier Estimate Liver Neoplasms / genetics Lymphocytes, Tumor-Infiltrating / immunology Polymorphism, Single Nucleotide Single-Cell Analysis

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
15 01 2020
Historique:
received: 17 01 2019
accepted: 13 12 2019
entrez: 17 1 2020
pubmed: 17 1 2020
medline: 14 4 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-019-14050-z PMID: 31941899 PMC: PMC6962317
pubmed: 31941899
doi: 10.1038/s41467-019-14050-z
pii: 10.1038/s41467-019-14050-z
pmc: PMC6962317
doi:

Substances chimiques

Epitopes 0
Hepatitis B Antigens 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

291

Subventions

Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA161373
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA078207
Pays : United States

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Auteurs

Bojan Losic (B)

Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Amanda J Craig (AJ)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Carlos Villacorta-Martin (C)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Sebastiao N Martins-Filho (SN)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Pathology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.

Nicholas Akers (N)

Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Adaptive Biotechnologies, Seattle, WA, USA.

Xintong Chen (X)

Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Mehmet E Ahsen (ME)

Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0002-4907-0427

Johann von Felden (J)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
ORCID: 0000-0003-2839-5174

Ismail Labgaa (I)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland.
ORCID: 0000-0003-4286-2170

Delia DʹAvola (D)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Liver Unit and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Clínica Universidad de Navarra, Pamplona, Spain.

Kimaada Allette (K)

Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Sergio A Lira (SA)

Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Glaucia C Furtado (GC)

Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Teresa Garcia-Lezana (T)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0002-7863-6784

Paula Restrepo (P)

Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Ashley Stueck (A)

Department of Pathology, Dalhousie University, Halifax, NS, Canada.

Stephen C Ward (SC)

Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Maria I Fiel (MI)

Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Spiros P Hiotis (SP)

Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Ganesh Gunasekaran (G)

Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Daniela Sia (D)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Eric E Schadt (EE)

Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sema4, a Mount Sinai venture, Stamford, CT, USA.
ORCID: 0000-0002-7892-8808

Robert Sebra (R)

Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sema4, a Mount Sinai venture, Stamford, CT, USA.

Myron Schwartz (M)

Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0002-9113-886X

Josep M Llovet (JM)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Liver Cancer Translational Research Laboratory, BCLC Group, IDIBAPS, Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain.
ORCID: 0000-0003-0547-2667

Swan Thung (S)

Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Gustavo Stolovitzky (G)

Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
IBM T. J. Watson Research Center, Yorktown Heights, New York, NY, USA.

Augusto Villanueva (A)

Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. augusto.villanueva@mssm.edu.
Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. augusto.villanueva@mssm.edu.
ORCID: 0000-0003-3585-3727

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Classifications MeSH

questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Carcinome hépatocellulaire › Intratumoral heterogeneity and clonal...
questionsmedicales.fr › Phénomènes génétiques › Évolution clonale › Intratumoral heterogeneity and clonal...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Intratumoral heterogeneity and clonal...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › Intratumoral heterogeneity and clonal...
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