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Genomic characterization of six virus-associated cancers identifies changes in the tumor microenvironment and altered genetic programming

Frederick S Varn, Yue Wang, View ORCID ProfileChao Cheng
doi: https://doi.org/10.1101/289900
Frederick S Varn
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth;
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Yue Wang
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth;
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Chao Cheng
Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth
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  • ORCID record for Chao Cheng
  • For correspondence: chao.cheng@dartmouth.edu
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Abstract

Viruses affect approximately 20% of all human cancers and induce the expression of viral oncoproteins that make these tumors potent targets for immune checkpoint inhibitors. In this study, we apply computational tools to The Cancer Genome Atlas and other datasets to define how virus infection shapes the tumor microenvironment and genetic architecture of 6 virus-associated tumor types. Across cancers, the cellular composition of the microenvironment varied by viral status, with infected tumors often exhibiting increased infiltration of cytolytic cell types. Analyses of the infiltrating T cell receptor repertoire revealed that Epstein-Barr virus was associated with decreased diversity in multiple cancers, suggesting an antigen-driven immune response. Tissue-specific gene expression signatures capturing these virus-induced transcriptomic changes successfully predicted virus status in independent datasets and were associated with both immune- and proliferation-related features that were predictive of prognosis. The analyses presented suggest viruses have distinct effects in different tumors with implications for immunotherapy.

Footnotes

  • Minor edits to language; Supplementary Table added containing MiTCR-based TCR diversity statistics.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 21, 2018.
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Genomic characterization of six virus-associated cancers identifies changes in the tumor microenvironment and altered genetic programming
Frederick S Varn, Yue Wang, Chao Cheng
bioRxiv 289900; doi: https://doi.org/10.1101/289900
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Genomic characterization of six virus-associated cancers identifies changes in the tumor microenvironment and altered genetic programming
Frederick S Varn, Yue Wang, Chao Cheng
bioRxiv 289900; doi: https://doi.org/10.1101/289900

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