LTR retroelement expansion of the human cancer transcriptome and immunopeptidome revealed by de novo transcript assembly. Jan Attig George R Young Louise Hosie David Perkins Vesela Encheva-Yokoya Jonathan P Stoye Ambrosius P Snijders Nicola Ternette George Kassiotis 10779/crick.11636799.v1 https://crick.figshare.com/articles/journal_contribution/LTR_retroelement_expansion_of_the_human_cancer_transcriptome_and_immunopeptidome_revealed_by_de_novo_transcript_assembly_/11636799 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. 2020-01-17 13:54:02 Kassiotis FC001099 Stoye FC001162 PRT SC-ack PC-ack 06 Biological Sciences 11 Medical and Health Sciences Bioinformatics