LTR retroelement expansion of the human cancer transcriptome and immunopeptidome revealed by de novo transcript assembly
- Jan Attig1,6,
- George R. Young2,6,
- Louise Hosie1,
- David Perkins3,
- Vesela Encheva-Yokoya3,
- Jonathan P. Stoye2,4,
- Ambrosius P. Snijders3,
- Nicola Ternette5 and
- George Kassiotis1,4
- 1Retroviral Immunology, The Francis Crick Institute, London NW1 1AT, United Kingdom;
- 2Retrovirus-Host Interactions, The Francis Crick Institute, London NW1 1AT, United Kingdom;
- 3Mass Spectrometry Proteomics, The Francis Crick Institute, London NW1 1AT, United Kingdom;
- 4Department of Medicine, Faculty of Medicine, Imperial College, London W2 1PG, United Kingdom;
- 5The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom
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↵6 These authors contributed equally to this work.
Abstract
Dysregulated endogenous retroelements (EREs) are increasingly implicated in the initiation, progression, and immune surveillance of human cancer. However, incomplete knowledge of ERE activity limits mechanistic studies. By using pan-cancer de novo transcript assembly, we uncover the extent and complexity of ERE transcription. The current assembly doubled the number of previously annotated transcripts overlapping with long-terminal repeat (LTR) elements, several thousand of which were expressed specifically in one or a few related cancer types. Exemplified in melanoma, LTR-overlapping transcripts were highly predictable, disease prognostic, and closely linked with molecularly defined subtypes. They further showed the potential to affect disease-relevant genes, as well as produce novel cancer-specific antigenic peptides. This extended view of LTR elements provides the framework for functional validation of affected genes and targets for cancer immunotherapy.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.248922.119.
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Freely available online through the Genome Research Open Access option.
- Received January 26, 2019.
- Accepted August 21, 2019.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
