Genome Res.-2019-Attig-1578-90.pdf (6.31 MB)

LTR retroelement expansion of the human cancer transcriptome and immunopeptidome revealed by de novo transcript assembly.

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posted on 17.01.2020 by Jan Attig, George R Young, Louise Hosie, David Perkins, Vesela Encheva-Yokoya, Jonathan P Stoye, Ambrosius P Snijders, Nicola Ternette, George Kassiotis
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.

Funding

Crick (Grant ID: 10162, Grant title: Stoye FC001162) Crick (Grant ID: 10099, Grant title: Kassiotis FC001099) Wellcome Trust (Grant ID: 102898/B/13/Z, Grant title: WT 102898/B/13/Z)

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