TY - JOUR A1 - Attig, Jan A1 - Young, George R. A1 - Hosie, Louise A1 - Perkins, David A1 - Encheva-Yokoya, Vesela A1 - Stoye, Jonathan P. A1 - Snijders, Ambrosius P. A1 - Ternette, Nicola A1 - Kassiotis, George T1 - LTR retroelement expansion of the human cancer transcriptome and immunopeptidome revealed by de novo transcript assembly Y1 - 2019/10/01 JF - Genome Research JO - Genome Research SP - 1578 EP - 1590 DO - 10.1101/gr.248922.119 VL - 29 IS - 10 UR - http://genome.cshlp.org/content/29/10/1578.abstract N2 - 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. ER -