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Intratumoral heterogeneity and clonal evolution in liver cancer.
- Source :
-
Nature communications [Nat Commun] 2020 Jan 15; Vol. 11 (1), pp. 291. Date of Electronic Publication: 2020 Jan 15. - Publication Year :
- 2020
-
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.
- Subjects :
- Carcinoma, Hepatocellular mortality
Carcinoma, Hepatocellular virology
DNA Copy Number Variations
Epitopes genetics
Epitopes immunology
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genetic Heterogeneity
Hepatitis B Antigens genetics
Hepatitis B virus genetics
Hepatitis B virus immunology
High-Throughput Nucleotide Sequencing
Humans
Kaplan-Meier Estimate
Liver Neoplasms mortality
Liver Neoplasms virology
Lymphocytes, Tumor-Infiltrating immunology
Lymphocytes, Tumor-Infiltrating pathology
Lymphocytes, Tumor-Infiltrating virology
Polymorphism, Single Nucleotide
Single-Cell Analysis
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular pathology
Clonal Evolution
Liver Neoplasms genetics
Liver Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31941899
- Full Text :
- https://doi.org/10.1038/s41467-019-14050-z