Intratumoral heterogeneity and clonal evolution in liver cancer
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...
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| Published in | Nature communications Vol. 11; no. 1; pp. 291 - 15 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
15.01.2020
Nature Publishing Group Nature Portfolio |
| Subjects | |
| Online Access | Get full text |
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| 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.
Immune-mediated selection pressures impact the clonal evolution of tumours. Here, in hepatocellular carcinoma the authors map spatio-temporal interactions between tumor and immune cells, highlighting the regulatory substrate of intra-tumoural heterogeneity that correlates with regional adaptive immune responses. |
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| AbstractList | 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.
Immune-mediated selection pressures impact the clonal evolution of tumours. Here, in hepatocellular carcinoma the authors map spatio-temporal interactions between tumor and immune cells, highlighting the regulatory substrate of intra-tumoural heterogeneity that correlates with regional adaptive immune responses. Immune-mediated selection pressures impact the clonal evolution of tumours. Here, in hepatocellular carcinoma the authors map spatio-temporal interactions between tumor and immune cells, highlighting the regulatory substrate of intra-tumoural heterogeneity that correlates with regional adaptive immune responses. 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. 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.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. 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.Immune-mediated selection pressures impact the clonal evolution of tumours. Here, in hepatocellular carcinoma the authors map spatio-temporal interactions between tumor and immune cells, highlighting the regulatory substrate of intra-tumoural heterogeneity that correlates with regional adaptive immune responses. |
| ArticleNumber | 291 |
| Author | Losic, Bojan Gunasekaran, Ganesh Sebra, Robert Lira, Sergio A. Sia, Daniela Villanueva, Augusto Hiotis, Spiros P. Schadt, Eric E. Villacorta-Martin, Carlos Restrepo, Paula Ward, Stephen C. Martins-Filho, Sebastiao N. Akers, Nicholas Fiel, Maria I. Schwartz, Myron Stolovitzky, Gustavo Stueck, Ashley Llovet, Josep M. Chen, Xintong von Felden, Johann Craig, Amanda J. Thung, Swan Labgaa, Ismail Furtado, Glaucia C. DʹAvola, Delia Allette, Kimaada Garcia-Lezana, Teresa Ahsen, Mehmet E. |
| Author_xml | – sequence: 1 givenname: Bojan surname: Losic fullname: Losic, Bojan organization: Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai – sequence: 2 givenname: Amanda J. surname: Craig fullname: Craig, Amanda J. organization: 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 – sequence: 3 givenname: Carlos surname: Villacorta-Martin fullname: Villacorta-Martin, Carlos organization: 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 – sequence: 4 givenname: Sebastiao N. surname: Martins-Filho fullname: Martins-Filho, Sebastiao N. organization: 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, Department of Pathology, University of Sao Paulo School of Medicine – sequence: 5 givenname: Nicholas surname: Akers fullname: Akers, Nicholas organization: Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Adaptive Biotechnologies – sequence: 6 givenname: Xintong surname: Chen fullname: Chen, Xintong organization: Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai – sequence: 7 givenname: Mehmet E. orcidid: 0000-0002-4907-0427 surname: Ahsen fullname: Ahsen, Mehmet E. organization: Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai – sequence: 8 givenname: Johann orcidid: 0000-0003-2839-5174 surname: von Felden fullname: von Felden, Johann organization: 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, I. Department of Medicine, University Medical Center Hamburg-Eppendorf – sequence: 9 givenname: Ismail orcidid: 0000-0003-4286-2170 surname: Labgaa fullname: Labgaa, Ismail organization: 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, Department of Visceral Surgery, Lausanne University Hospital CHUV – sequence: 10 givenname: Delia surname: DʹAvola fullname: DʹAvola, Delia organization: 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, Liver Unit and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Clínica Universidad de Navarra – sequence: 11 givenname: Kimaada surname: Allette fullname: Allette, Kimaada organization: Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai – sequence: 12 givenname: Sergio A. surname: Lira fullname: Lira, Sergio A. organization: Immunology Institute, Icahn School of Medicine at Mount Sinai – sequence: 13 givenname: Glaucia C. surname: Furtado fullname: Furtado, Glaucia C. organization: Immunology Institute, Icahn School of Medicine at Mount Sinai – sequence: 14 givenname: Teresa orcidid: 0000-0002-7863-6784 surname: Garcia-Lezana fullname: Garcia-Lezana, Teresa organization: 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 – sequence: 15 givenname: Paula surname: Restrepo fullname: Restrepo, Paula organization: Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai – sequence: 16 givenname: Ashley surname: Stueck fullname: Stueck, Ashley organization: Department of Pathology, Dalhousie University – sequence: 17 givenname: Stephen C. surname: Ward fullname: Ward, Stephen C. organization: Department of Pathology, Icahn School of Medicine at Mount Sinai – sequence: 18 givenname: Maria I. surname: Fiel fullname: Fiel, Maria I. organization: Department of Pathology, Icahn School of Medicine at Mount Sinai – sequence: 19 givenname: Spiros P. surname: Hiotis fullname: Hiotis, Spiros P. organization: Department of Surgery, Icahn School of Medicine at Mount Sinai – sequence: 20 givenname: Ganesh surname: Gunasekaran fullname: Gunasekaran, Ganesh organization: Department of Surgery, Icahn School of Medicine at Mount Sinai – sequence: 21 givenname: Daniela surname: Sia fullname: Sia, Daniela organization: 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 – sequence: 22 givenname: Eric E. orcidid: 0000-0002-7892-8808 surname: Schadt fullname: Schadt, Eric E. organization: Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, Sema4, a Mount Sinai venture – sequence: 23 givenname: Robert surname: Sebra fullname: Sebra, Robert organization: Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, Sema4, a Mount Sinai venture – sequence: 24 givenname: Myron orcidid: 0000-0002-9113-886X surname: Schwartz fullname: Schwartz, Myron organization: Department of Surgery, Icahn School of Medicine at Mount Sinai – sequence: 25 givenname: Josep M. orcidid: 0000-0003-0547-2667 surname: Llovet fullname: Llovet, Josep M. organization: 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, Liver Cancer Translational Research Laboratory, BCLC Group, IDIBAPS, Hospital Clinic, Universitat de Barcelona, Institució Catalana de Recerca i Estudis Avançats – sequence: 26 givenname: Swan surname: Thung fullname: Thung, Swan organization: Department of Pathology, Icahn School of Medicine at Mount Sinai – sequence: 27 givenname: Gustavo surname: Stolovitzky fullname: Stolovitzky, Gustavo organization: Department of Genetics and Genomic Sciences, Cancer Immunology Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, IBM T. J. Watson Research Center, Yorktown Heights – sequence: 28 givenname: Augusto orcidid: 0000-0003-3585-3727 surname: Villanueva fullname: Villanueva, Augusto email: augusto.villanueva@mssm.edu organization: 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, Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31941899$$D View this record in MEDLINE/PubMed |
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| Snippet | Clonal evolution of a tumor ecosystem depends on different selection pressures that are principally immune and treatment mediated. We integrate RNA-seq, DNA... Immune-mediated selection pressures impact the clonal evolution of tumours. Here, in hepatocellular carcinoma the authors map spatio-temporal interactions... |
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| SubjectTerms | 38/23 45 45/91 631/250 631/67 692/4020 692/4028 Adaptive immunity Adaptive systems Antigens Biopsy Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - mortality Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - virology Clonal Evolution Deoxyribonucleic acid DNA DNA Copy Number Variations DNA sequencing Epitopes Epitopes - genetics Epitopes - immunology Evolution Gene expression Gene Expression Regulation, Neoplastic Gene Regulatory Networks Genetic Heterogeneity Hepatitis B Hepatitis B Antigens - genetics Hepatitis B virus - genetics Hepatitis B virus - immunology Hepatocellular carcinoma Heterogeneity High-Throughput Nucleotide Sequencing Humanities and Social Sciences Humans Immune response Immune system Kaplan-Meier Estimate Liver Liver cancer Liver Neoplasms - genetics Liver Neoplasms - mortality Liver Neoplasms - pathology Liver Neoplasms - virology Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - pathology Lymphocytes, Tumor-Infiltrating - virology multidisciplinary Mutation Polymorphism, Single Nucleotide Ribonucleic acid RNA Science Science (multidisciplinary) Single-Cell Analysis Single-nucleotide polymorphism Substrates Survival T cell receptors Transcriptomics Tumors Viruses |
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| Title | Intratumoral heterogeneity and clonal evolution in liver cancer |
| URI | https://link.springer.com/article/10.1038/s41467-019-14050-z https://www.ncbi.nlm.nih.gov/pubmed/31941899 https://www.proquest.com/docview/2342441729 https://www.proquest.com/docview/2339793975 https://pubmed.ncbi.nlm.nih.gov/PMC6962317 https://doaj.org/article/b7e9387e6d0443a18b41f98ca9cd0d20 |
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