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Intratumoral heterogeneity and clonal evolution in liver cancer.

Authors :
Losic B
Craig AJ
Villacorta-Martin C
Martins-Filho SN
Akers N
Chen X
Ahsen ME
von Felden J
Labgaa I
DʹAvola D
Allette K
Lira SA
Furtado GC
Garcia-Lezana T
Restrepo P
Stueck A
Ward SC
Fiel MI
Hiotis SP
Gunasekaran G
Sia D
Schadt EE
Sebra R
Schwartz M
Llovet JM
Thung S
Stolovitzky G
Villanueva A
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.

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