Shelterin complex gene: Prognosis and therapeutic vulnerability in cancer

Abstract

Telomere encompasses a (TTAGGG)n tandem repeats, and its dysfunction has emerged as the epicenter of driving carcinogenesis by promoting genetic instability. Indeed, they play an essential role in stabilizing chromosomes and therefore protecting them from end-to-end fusion and DNA degradation. Telomere length homeostasis is regulated by several key players including shelterin complex genes, telomerase, and various other regulators. Targeting these regulatory players can be a good approach to combat cancer as telomere length is increasingly correlated with cancer initiation and progression. In this review, we have aimed to describe the telomere length regulator's role in prognostic significance and important drug targets in breast cancer. Moreover, we also assessed alteration in telomeric function by various telomere length regulators and compares this to the regulatory mechanisms that can be associated with clinical biomarkers in cancer. Using publicly available software we summarized mutational and CpG island prediction analysis of the TERT gene breast cancer patient database. Studies have reported that the TERT gene has prognostic significance in breast cancer progression however mechanistic approaches are not defined yet. Interestingly, we reported using the UCSC Xena web-based tool, we confirmed a positive correlation of shelterin complex genes TERF1 and TERF2 in recurrent free survival, indicating the critical role of these genes in breast cancer prognosis. Moreover, the epigenetic landscape of DNA damage repair genes in different breast cancer subtypes also being analyzed using the UCSC Xena database. Together, these datasets provide a comprehensive resource for shelterin complex gene profiles and define epigenetic landscapes of DNA damage repair genes which reveals the key role of shelterin complex genes in breast cancer with the potential to identify novel and actionable targets for treatment.

Keywords

• Telomere
• DNA damage
• hTERT
• Shelterin complex