Abstract
Merkel Cell Carcinoma (MCC) is a rare but highly aggressive form of non–melanoma skin cancer whose 5-year survival rate is 63%. Merkel cell polyomavirus (MCPyV), a small DNA tumor virus, is the etiological agent of MCC. Although representing a small proportion of MCC cases, MCPyV-negative MCCs have also been identified. The role of epigenetic mechanisms, including histone post-translational modifications (PTMs) in MCC, have been only partially determined. This review aims to describe the most recent progress on PTMs and their regulative factors in the context of MCC onset/development, providing an overview of current findings on both MCC subtypes. An outline of current knowledge on the potential employment of PTMs and related factors as diagnostic and prognostic markers, as well as novel treatment strategies targeting the reversibility of PTMs for MCC therapy is provided. Recent research shows that PTMs are emerging as important epigenetic players involved in MCC onset/development, and therefore may show a potential clinical significance. Deeper and integrated knowledge of currently known PTM dysregulations is of paramount importance in order to understand the molecular basis of MCC and improve the diagnosis, prognosis, and therapeutic options for this deadly tumor.
Highlights
Merkel cell carcinoma (MCC) is a rare, but aggressive non–melanoma skin cancer [1–3]
Phosphorylation of other DNA damage response (DDR)/ataxia telangiectasia mutant (ATM) downstream proteins has been described. These findings cumulatively suggest the contribution of histone methylation and phosphorylation in Merkel cell polyomavirus (MCPyV) small T antigen (sT)-induced DDR pathway activation upon MCCP onset [104]
This review summarizes and provides insights into post-translational modifications (PTMs) and related factors being assessed as linked to MCC (Figure 1)
Summary
Merkel cell carcinoma (MCC) is a rare, but aggressive non–melanoma skin cancer [1–3]. Similar presentation and prognosis, two different MCC aetiologies have been identified. The first, which accounts for the highest proportion [4–8], ~80% of cases, is caused by a DNA tumor virus belonging to the polyomaviridae family, i.e., Merkel cell polyomavirus (MCPyV) [2, 9]. The expression of the two viral oncoproteins truncated large T antigen (tLT) and small T antigen (sT), alongside the integration of the MCPyV DNA into the host genome, are the main events for MCPyV-positive MCC (MCCP) onset [9–12]. In MCCP cells, LT expression leads to cell proliferation maintenance [13], while sT is required for cell transformation and survival [14].
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