Abstract
The role of telomere biology and telomerase activation in skin cancers has been investigated in melanoma and basal cell carcinoma but limited evidence is available for cutaneous squamous cell carcinoma (cSCC). We will review the current knowledge on the role of telomere and telomerase pathway in cSCC pathogenesis. At the somatic level, both long and short telomere lengths have been described in cSCC. This telomere dichotomy is probably related to two different mechanisms of tumour initiation which determines two tumour subtypes. Telomere shortening is observed during the invasive progression from in situ forms of cSCC, such as Bowen’s disease (BD) and actinic keratosis (AK), to invasive cSCC. At the germline level, controversial results have been reported on the association between constitutive telomere length and risk of cSCC. Approximately 75–85% of cSCC tumours are characterized by a high level of telomerase activity. Telomerase activation has been also reported in AKs and BD and in sun-damaged skin, thus supporting the hypothesis that UV modulates telomerase activity in the skin. Activating TERT promoter mutations have been identified in 32–70% of cSCCs, with the majority showing the UV-signature. No significant correlation was observed between TERT promoter mutations and cSCC clinico-pathological features. However, TERT promoter mutations have been recently suggested to be independent predictors of an adverse outcome. The attention on telomere biology and telomerase activity in cSCC is increasing for the potential implications in the development of effective tools for prognostic assessment and of therapeutic strategies in patients with cutaneous cSCC.
Highlights
Cutaneous squamous cell carcinoma accounts for 20% of all non-melanoma skin cancers (NMSCs) and is the second most common NMSC in white populations [1,2]
Telomere and Telomerase Activity in Cutaneous Squamous Cell Carcinoma Cutaneous squamous cell carcinoma (cSCC) are characterized by a high frequency of chromosomal aberrations and a high level of genomic instability [73], which might be related to telomere biology alteration [74]
AK, actinic keratosis; BD, Bowen’s disease; cSCC, squamous cell carcinoma; TERT, Telomerase reverse transcriptase. It is still a matter of debate how telomere biology and telomerase activation contribute to skin carcinogenesis and controversial results have been reported for cSCC, mainly due to limited available evidences
Summary
Cutaneous squamous cell carcinoma (cSCC) accounts for 20% of all non-melanoma skin cancers (NMSCs) and is the second most common NMSC in white populations [1,2]. Fair skin type and chronic exposure to ultraviolet (UV) radiation are the major risk factors for the development of cSCC with 90% of the tumours arising on sun-exposed areas such as the head and neck region, dorsum of the hands and the forearms [6,7]. Several studies support the role of telomere biology and telomerase activation in the development of malignant skin cancers. It has been extensively reported in melanoma and, more recently, in basal cell carcinoma (BCC), while limited data are available in cSCC [16,17,18,19,20]. We will summarize the current knowledge about the role of telomere and telomerase pathway in cSCC pathogenesis
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