Poster #70 - Ayna Mammedova

Pan-Cancer Analysis of Transposable Element Expression Reveals Cancer Type-Specific Patterns

Mammedova A, MS 1; Calendo G, MS 1; Issa, JPJ, MD 1 Affiliations: 1 Coriell Institute for Medical Research, Camden, NJ, USA

Transposable elements (TEs) comprise nearly half of the human genome and are normally silenced in healthy cells through DNA methylation and other epigenetic mechanisms. Recent evidence suggests that epigenetic dysregulation of TEs during tumorigenesis not only drives oncogenic processes but may also provide novel therapeutic targets and prognostic biomarkers. Despite their abundance and potential importance, TE expression patterns across different cancer types remain poorly characterized. We analyzed TE expression across ~1,100 TE subfamilies in ~1,000 cancer cell lines representing ~40 different cancer types from CCLE to systematically characterize cancer-specific TE dysregulation patterns. UMAP analysis of TE expression revealed clear cancer type separation based on TE expression profiles. Hematological malignancies (lymphoma, myeloma, leukemia) exhibited significantly elevated mean TE expression, while normal fibroblasts showed the lowest levels. Gene Ontology analysis of genes correlated with TE expression z-scores revealed that positively correlated genes (r ≥ 0.5) were enriched for RNA splicing and mRNA processing pathways, while negatively correlated genes (r ≤ -0.5) participated in protein synthesis and degradation processes. Additionally, cancer driver gene mutations showed significant associations with altered TE expression patterns. These preliminary findings establish TE expression as a robust, cancer type-specific molecular signature with connections to RNA processing machinery. Ongoing analyses using TCGA tumor cohorts will validate these findings in primary cancers and assess their utility for classification and biomarker development.