Melanoma: Stem cells, sun exposure and hallmarks for carcinogenesis, molecular concepts and future clinical implications

Athanassios Kyrgidis1, Thrasivoulos-George Tzellos2, Stefanos Triaridis3
1Departments of Otolaryngology, Head & Neck Surgery and Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

2Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
3Department of Otolaryngology, Head & Neck Surgery, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.


Background: The classification and prognostic assessment of melanoma is currently based on morphologic and histopathologic biomarkers. Availability of an increasing number of molecular biomarkers provides the potential for redefining diagnostic and prognostic categories and utilizing pharmacogenomics for the treatment of patients. The aim of the present review is to provide a basis that will allow the construction-or reconstruction-of future melanoma research. Methods: We critically review the common medical databases (PubMed, EMBASE, Scopus and Cochrane CENTRAL) for studies reporting on molecular biomarkers for melanoma. Results are discussed along the hallmarks proposed for malignant transformation by Hanahan and Weinberg. We further discuss the genetic basis of melanoma with regard to the possible stem cell origin of melanoma cells and the role of sunlight in melanoma carcinogenesis. Results: Melanocyte precursors undergo several genome changes -UV-induced or not- which could be either mutations or epigenetic. These changes provide stem cells with abilities to self-invoke growth signals, to suppress anti-growth signals, to avoid apoptosis, to replicate without limit, to invade, proliferate and sustain angiogenesis. Melanocyte stem cells are able to progressively collect these changes in their genome. These new potential functions, drive melanocyte precursors to the epidermis were they proliferate and might cause benign nevi. In the epidermis, they are still capable of acquiring new traits via changes to their genome. With time, such changes could add up to transform a melanocyte precursor to a malignant melanoma stem cell. Conclusions : Melanoma cannot be considered a “black box” for researchers anymore. Current trends in the diagnosis and prognosis of melanoma are to individualize treatment based on molecular biomarkers. Pharmacogenomics constitute a promising field with regard to melanoma patients’ treatment. Finally, development of novel monoclonal antibodies is expected to complement melanoma patient care while a number of investigational vaccines could find their way into everyday oncology practice.

Keywords: Biomarkers, carcinogenesis, melanoma, melanomagenesis, stem cells, sunlight, ultra violet light exposure