Alternative splicing of transposable elements in human breast cancer

Transposable elements (TEs) are an important driver of genome evolution and can affect gene expression through diverse mechanisms. In breast cancer, disrupted TE sequence regulation may facilitate tumor-specific transcriptomic alterations. Our study utilized long-read RNA sequencing (LR-seq) from 30 breast samples (142,514 full-length isoforms) to examine the effects of TEs on the breast cancer transcriptome. We identified hundreds of unique transcription start sites, splice sites, and termination sites within or adjacent to TEs. Our examination of TEs in the context of post-transcriptionalRNA editing revealed thousands of isoforms with editing signatures, including a novel RHOA isoform implicated in lung tumor progression. Polymorphic TE insertions are a source of genomic variation amongst individuals and have the potential to alter splicing.The full-length isoforms captured by long-reads enabled us to identify spliced TEs that are unique to individuals with the insertion. Together, our results demonstrate the widespread effects of dysregulated TEs on breast cancer transcriptomes and the advantages of long-read isoform sequencing for understanding TE biology. TE isoforms may alter the expression of genes important in cancer and could potentially be used as novel, disease-specific, therapeutic targets.