Abstract
Melanoma is a deadly skin cancer that becomes especially difficult to treat after it metastasizes. Timely identification of melanoma is critical for effective therapy, but histopathologic diagnosis can frequently pose a significant challenge to this goal. Therefore, auxiliary diagnostic tools are imperative to facilitating prompt recognition of malignant lesions. Melanoma develops as result of a number of genetic mutations, with UV radiation often acting as a mutagenic risk factor. Novel methods of genetic testing have improved detection of these molecular alterations, which subsequently revealed important information for diagnosis and prognosis. Rapid detection of genetic alterations is also significant for choosing appropriate treatment and developing targeted therapies for melanoma. This review will delve into the understanding of various mutations and the implications they may pose for clinical decision making.
Highlights
Melanoma represents the most lethal type of skin cancer, with an estimated 7000 deaths in 2019 in the United States [1]
While vitamin D receptor (VDR) expression was not found to be associated with histopathological characteristics of uveal melanoma, an inverse correlation was shown between expression level and the degree of tumor pigmentation [150]
VDR expression has been shown to be negatively correlated with overall prognosis in melanoma patients, painting an important picture for vitamin D-based therapy [23,24,140]
Summary
Melanoma represents the most lethal type of skin cancer, with an estimated 7000 deaths in 2019 in the United States [1]. Ultraviolet radiation (UVR) represents a major contributor to cutaneous melanomagenesis through its deleterious effects on the skin and direct damage to DNA [3] These processes trigger the acceleration of tumorigenesis and have facilitated the emergence of malignant melanoma as a significant public health problem. Uveal melanoma has an estimated annual incidence of 5.1 cases per million and comprises approximately 3%–5% of all melanomas [8,9,10] Relatively rare, this malignancy is highly lethal due to its rapidly metastatic nature. Diagnostic and therapeutic molecular markers have been increasingly used to assist in histopathological assessment of these tumors These markers are helpful for diagnosing melanoma, and in distinguishing certain subtypes that may otherwise be difficult to identify (Table 1). None [70,71,72] Phase II trial of PARP inhibitor, niraparib (NCT03207347) [73,74] None [34,75] None [34,76]
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