Current molecular and clinical insights into uveal melanoma (Review)

Abstract

Uveal melanoma (UM) represents the most prominent primary eye cancer in adults. With an incidence of approximately 5 cases per million individuals annually in the United States, UM could be considered a relatively rare cancer. The 90‑95% of UM cases arise from the choroid. Diagnosis is based mainly on a clinical examination and ancillary tests, with ocular ultrasonography being of greatest value. Differential diagnosis can prove challenging in the case of indeterminate choroidal lesions and, sometimes, monitoring for documented growth may be the proper approach. Fine needle aspiration biopsy tends to be performed with a prognostic purpose, often in combination with radiotherapy. Gene expression profiling has allowed for the grading of UMs into two classes, which feature different metastatic risks. Patients with UM require a specialized multidisciplinary management. Primary tumor treatment can be either enucleation or globe preserving. Usually, enucleation is reserved for larger tumors, while radiotherapy is preferred for small/medium melanomas. The prognosis is unfavorable due to the high mortality rate and high tendency to metastasize. Following the development of metastatic disease, the mortality rate increases to 80% within one year, due to both the absence of an effective treatment and the aggressiveness of the condition. Novel molecular studies have allowed for a better understanding of the genetic and epigenetic mechanisms involved in UM biological activity, which differs compared to skin melanomas. The most commonly mutated genes are GNAQ, GNA11 and BAP1. Research in this field could help to identify effective diagnostic and prognostic biomarkers, as well as novel therapeutic targets.

Keywords: uveal melanoma; staging; treatment; diagnosis; prognosis; biomarkers; epigenetics.

Figure 1

Schematic representation of the genetic and epigenetic alterations and risk factors involved in the development of uveal melanoma. Environmental and individual risk factors (including age, sex and ethnicity) are able to induce both genetic and epigenetic modifications responsible for the malignant transformation of choroid cells. Clinical and prognostic assessment could benefit from the analysis of genetic and epigenetic factors associated with the development of uveal melanoma.