Implications of TERT promoter mutations and telomerase activity in solid tumors with a focus on genitourinary cancers

ABSTRACT

Introduction

The reactivation of telomerase represents a key moment in the carcinogenesis process. Mutations in the central promoter region of the telomerase reverse transcriptase (TERT) gene cause telomerase reactivation in approximately 90% of solid tumors. In some of these, its prognostic and predictive role in response to treatments has already been demonstrated, in others (such as tumors of the genitourinary tract like urothelial carcinoma) data are controversial and the research is still ongoing. In the future, TERT promoter mutations and telomerase activity could have diagnostic, prognostic, and therapeutic applications in many types of cancer.

Areas covered

We performed a review the literature with the aim of describing the current evidence on the prognostic and predictive role of TERT promoter mutations. In some tumor types, TERT promoter mutations have been associated with a worse prognosis and could have a potential value as biomarkers to guide therapeutic decisions. Mutations in TERT promoter seems to make the tumor particularly immunogenic and more responsive to immunotherapy, although data is controversial.

Expert opinion

We described the role of TERT promoter mutations in solid tumors with a particular focus in genitourinary cancers, considering their frequency in this tract.

KEYWORDS:

• Telomerase
• TERT
• carcinogenesis
• glioma
• urothelial carcinoma
• genitourinary
• ICI
• immunotherapy

Article highlights

• The telomerase system dedicated to telomere protection and homeostasis ensures the balance between genomic integrity, aging, and cancer.

• TERT is a cornerstone of carcinogenesis, and mutations in the promoter region cause telomerase reactivation in approximately 90% of solid tumors. It may have prognostic and diagnostic implications in several tumor types.

• In gliomas, both low- and high-grade, TERT promoter mutation has a pivotal prognostic value and seems to retain also a predictive role.

• TERT promoter mutation is extremely frequent in urothelial carcinoma, being altered in up to 66% of muscle-invasive forms.

• TERT promoter alterations may have a prognostic or predictive role even in advanced disease, thus potentially helping to select patients who are most likely to respond to a specific treatment.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.