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Title: Intratumoral heterogeneity and clonal evolution in liver cancer
Author: Losic, Bojan
Craig, Amanda J.
Villacorta-Martin, Carlos
Martins-Filho, Sebastiao N.
Akers, Nicholas
Chen, Xintong
Ahsen, Mehmet Eren
Felden, Johann von
Labgaa, Ismail
Avola, Delia D'
Allette, Kimaada
Lira, Sergio A.
Furtado, Glaucia C.
Garcia-Lezana, Teresa
Restrepo, Paula
Stueck, Ashley
Ward, Stephen C.
Fiel, Maria I.
Hiotis, Spiros P.
Gunasekaran, Ganesh
Sia, Daniela
Schadt, Eric E.
Sebra, Robert
Schwartz, Myron
Llovet i Bayer, Josep Maria
Thung, Swan
Stolovitzky, Gustavo
Villanueva, Augusto
Keywords: Càncer de fetge
Genètica molecular humana
Liver cancer
Human molecular genetics
Issue Date: 15-Jan-2020
Publisher: Nature Publishing Group
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.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2020, vol. 11, num. 291
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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