Intratumoral heterogeneity and clonal evolution in liver cancer

Bojan Losic, Amanda J. Craig, Carlos Villacorta-Martin, Sebastiao N. Martins-Filho, Nicholas Akers, Xintong Chen, Mehmet E. Ahsen, Johann Felden, Ismail Labgaa, Delia DʹAvola, Kimaada Allette, Sergio A. Lira, Glaucia C. Furtado, Teresa Garcia-Lezana, Paula Restrepo, Ashley Stueck, Stephen C. Ward, Maria I. Fiel, Spiros P. Hiotis, Ganesh Gunasekaran, Daniela Sia, Eric E. Schadt, Robert Sebra, Myron Schwartz, Josep M. Llovet, Swan Thung, Gustavo Stolovitzky and Augusto Villanueva ()
Additional contact information
Bojan Losic: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Amanda J. Craig: Icahn School of Medicine at Mount Sinai
Carlos Villacorta-Martin: Icahn School of Medicine at Mount Sinai
Sebastiao N. Martins-Filho: Icahn School of Medicine at Mount Sinai
Nicholas Akers: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Xintong Chen: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Mehmet E. Ahsen: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Johann Felden: Icahn School of Medicine at Mount Sinai
Ismail Labgaa: Icahn School of Medicine at Mount Sinai
Delia DʹAvola: Icahn School of Medicine at Mount Sinai
Kimaada Allette: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Sergio A. Lira: Icahn School of Medicine at Mount Sinai
Glaucia C. Furtado: Icahn School of Medicine at Mount Sinai
Teresa Garcia-Lezana: Icahn School of Medicine at Mount Sinai
Paula Restrepo: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Ashley Stueck: Dalhousie University
Stephen C. Ward: Icahn School of Medicine at Mount Sinai
Maria I. Fiel: Icahn School of Medicine at Mount Sinai
Spiros P. Hiotis: Icahn School of Medicine at Mount Sinai
Ganesh Gunasekaran: Icahn School of Medicine at Mount Sinai
Daniela Sia: Icahn School of Medicine at Mount Sinai
Eric E. Schadt: Icahn School of Medicine at Mount Sinai
Robert Sebra: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Myron Schwartz: Icahn School of Medicine at Mount Sinai
Josep M. Llovet: Icahn School of Medicine at Mount Sinai
Swan Thung: Icahn School of Medicine at Mount Sinai
Gustavo Stolovitzky: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Augusto Villanueva: Icahn School of Medicine at Mount Sinai

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-019-14050-z

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