Detalle Publicación

Intratumoral heterogeneity and clonal evolution in liver cancer

Autores: Losic, B.; Craig, A. J.; Villacorta-Martin, C.; Martins, S. N.; Akers, N.; Chen, X. T.; Ahsen, M. E.; von-Felden, J.; Labgaa, I.; D'Avola, Delia; Allette, K.; Lira, S. A.; Furtado, G. C.; García-Lezana, T.; Restrepo, P.; Stueck, A.; Ward, S. C.; Fiel, M. I.; Hiotis, S. P.; Gunasekaran, G.; Sia, D.; Schadt, E. E.; Sebra, R.; Schwartz, M.; Llovet, J. M.; Thung, S.; Stolovitzky, G.; Villanueva, A.
Título de la revista: NATURE COMMUNICATIONS
ISSN: 2041-1723
Volumen: 11
Número: 1
Páginas: 291
Fecha de publicación: 2020
Resumen:
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.
DOI: https://doi.org/10.1038/s41467-019-14050-z
Impacto:
215 citas en
Google Scholar