Pan-Cancer Analysis of Telomerase Reverse Transcriptase (TERT) Isoforms
Abstract
Reactivation of the multi-subunit ribonucleoprotein telomerase is the primary telomere maintenance mechanism in cancer, but it is rate-limited by the enzymatic component, telomerase reverse transcriptase (TERT). While regulatory in nature, TERT alternative splice variant/isoform regulation and functions are not fully elucidated and are further complicated by their highly diverse expression. In this thesis, I characterized TERT expression across normal and neoplastic tissues using TCGA and GTEx RNA-sequencing data. In doing so, I demonstrated the global overexpression and splicing shift towards full-length TERT in neoplastic tissue. Furthermore, my studies identified tumour subtype expression differences possibly regulated by subtype-specific characteristics, detailed heterogeneity in both isoform function and prognostic potential and determined cancer cell lines with representative tumour specific TERT transcriptomes. Taken together, my work reinforced the need for tissue specific TERT investigations, provided avenues to do so, and brought to light the current technical limitations of bioinformatically analyzing TERT isoform expression.