Pan-cancer Experimental Characteristic of Human Transcriptional Patterns Connected with Telomerase Reverse Transcriptase () Gene Expression Status

The gene encodes the reverse transcriptase subunit of telomerase and is normally transcriptionally suppressed in differentiated human cells but reactivated in cancers where its expression is frequently associated with poor survival prognosis. Here we experimentally assessed the RNA sequencing expression patterns associated with transcription in 1039 human cancer samples of 27 tumor types. We observed a bimodal distribution of expression where ∼27% of cancer samples did not express and the rest showed a bell-shaped distribution. Expression of strongly correlated with 1443 human genes including 103 encoding transcriptional factor proteins. Comparison of - positive and negative cancers showed the differential activation of 496 genes and 1975 molecular pathways. Therein, 32/38 (84%) of DNA repair pathways were hyperactivated in cancers which was also connected with accelerated replication, transcription, translation, and cell cycle progression. In contrast, the level of 40 positive cell cycle regulator proteins and a set of epithelial-to-mesenchymal transition pathways was specific for the group suggesting different proliferation strategies for both groups of cancer. Our pilot study showed that the group had ∼13% of cancers with or mutated promoter. However, the presence of promoter mutations was not associated with greater expression compared with other cancers, suggesting parallel mechanisms of its transcriptional activation in cancers. In addition, we detected a decreased expression of L1 retrotransposons in the group, and further decreased L1 expression in promoter mutated cancers. expression was correlated with 17 genes encoding molecular targets of cancer therapeutics and may relate to differential survival patterns of - positive and negative cancers.