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

Journal Article: Genome ResearchYear Published: (2019) Volume Number: 29, Article Number: 1578-1590

Authors

Attig,Jan; Young,George R; Hosie,Louise; Perkins,David; Encheva-Yokoya,Vesela; Stoye,Jonathan P; Snijders,Ambrosius P; Ternette,Nicola; Kassiotis,George

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.