Telomere Maintenance

Telomere maintenance is a hallmark of human cancer. In the majority of human cancer, telomere maintenance is achieved by reactivation of telomerase. TERT – a reverse transcriptase component of telomerase – is a proto-oncogene that governs the telomerase activity and is transcriptionally dysregulated in cancer. While genetic alterations including mutations affecting the TERT promoter has been described, the exact mechanism of TERT reactivation in human cancer cells remains poorly understood.

We aim to investigate an aberrant DNA hypermethylation signature within the TERT promoter observed uniquely in human cancer. Our lab had uncovered a cancer-specific DNA hypermethylated region within the TERT promoter – defined as the TERT Hypermethylated Oncological Region (THOR) – and showed high prevalence of this epigenetic alteration in the context of human cancer.

Currently, we are working to understand biological and clinical implications of THOR hypermethylation, leading to its potency as a therapeutic target and a diagnostic biomarker. We are also in the process of establishing a new model of differential allelic THOR hypermethylation in human cancer and how it can explain differential allelic expression of TERT.

Together, our work provide an insight into the DNA methylation landscape of the TERT promoter, introduce a THOR-dependent TERT upregulatory mechanism, and propose therapeutic and diagnostic potential of THOR hypermethylation signature.


Telomere Maintenance Team