The Emerging Burden of Genetic Instability and Mutation in Melanoma: Role of Molecular Mechanisms

SIMPLE SUMMARY: Melanoma is a severe skin cancer affecting thousands of people and a growing public health concern worldwide. The potential hallmarks of melanoma are genetic instability and mutation (GIAM), which is the crucial vulnerability of cancer cells, determining their sensitivity to harmful treatments, including radiation and many chemotherapeutics. Therefore, the ability of cells to sense DNA damage and respond appropriately is an essential aspect of genome maintenance. ABSTRACT: Melanoma is a severe skin cancer affecting thousands of people and a growing public health concern worldwide. The potential hallmarks of melanoma are genetic instability and mutation (GIAM), which are driving mechanisms for phenotypic variation and adaptation in melanoma. In metastatic melanoma, DNA repair-associated genes are frequently expressed at higher levels than in primary cancers, suggesting melanoma cells rely on genetic stability to spread distantly. The tumour microenvironment is affected by genomic instability and melanoma mutation (GIMM), which plays significant roles in developing GIMM and their contributions to the overall disease burden. The GIAM is the crucial vulnerability of cancer cells, determining their sensitivity to harmful treatments, including radiation and many chemotherapeutics. The high incidence of melanoma is typically associated with genetic modifications, and several clinical and genetic interventions have been critical in easing the burden.