Intratumoral heterogeneity and clonal evolution in liver cancer.
Détails
ID Serval
serval:BIB_6DA7AC29DA7C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Intratumoral heterogeneity and clonal evolution in liver cancer.
Périodique
Nature communications
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
15/01/2020
Peer-reviewed
Oui
Volume
11
Numéro
1
Pages
291
Langue
anglais
Notes
Publication types: 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.
Publication Status: epublish
Publication Status: 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.
Mots-clé
Carcinoma, Hepatocellular/genetics, Carcinoma, Hepatocellular/mortality, Carcinoma, Hepatocellular/pathology, Carcinoma, Hepatocellular/virology, Clonal Evolution, 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/genetics, Liver Neoplasms/mortality, Liver Neoplasms/pathology, Liver Neoplasms/virology, Lymphocytes, Tumor-Infiltrating/immunology, Lymphocytes, Tumor-Infiltrating/pathology, Lymphocytes, Tumor-Infiltrating/virology, Polymorphism, Single Nucleotide, Single-Cell Analysis
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/01/2020 16:57
Dernière modification de la notice
10/02/2024 8:16