Intratumoral heterogeneity and clonal evolution in liver cancer
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Intratumoral heterogeneity and clonal evolution in liver cancer. / Losic, Bojan; Craig, Amanda J; Villacorta-Martin, Carlos; Martins-Filho, Sebastiao N; Akers, Nicholas; Chen, Xintong; Ahsen, Mehmet E; von Felden, Johann; Labgaa, Ismail; DʹAvola, Delia; 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, Josep M; Thung, Swan; Stolovitzky, Gustavo; Villanueva, Augusto.
In: NAT COMMUN, Vol. 11, No. 1, 15.01.2020, p. 291.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Intratumoral heterogeneity and clonal evolution in liver cancer
AU - Losic, Bojan
AU - Craig, Amanda J
AU - Villacorta-Martin, Carlos
AU - Martins-Filho, Sebastiao N
AU - Akers, Nicholas
AU - Chen, Xintong
AU - Ahsen, Mehmet E
AU - von Felden, Johann
AU - Labgaa, Ismail
AU - DʹAvola, Delia
AU - Allette, Kimaada
AU - Lira, Sergio A
AU - Furtado, Glaucia C
AU - Garcia-Lezana, Teresa
AU - Restrepo, Paula
AU - Stueck, Ashley
AU - Ward, Stephen C
AU - Fiel, Maria I
AU - Hiotis, Spiros P
AU - Gunasekaran, Ganesh
AU - Sia, Daniela
AU - Schadt, Eric E
AU - Sebra, Robert
AU - Schwartz, Myron
AU - Llovet, Josep M
AU - Thung, Swan
AU - Stolovitzky, Gustavo
AU - Villanueva, Augusto
PY - 2020/1/15
Y1 - 2020/1/15
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-019-14050-z
DO - 10.1038/s41467-019-14050-z
M3 - SCORING: Journal article
C2 - 31941899
VL - 11
SP - 291
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -