The tumor genetics of acral melanoma- what should a dermatologist know?

Abstract Dermatologists stand at the gateway of individualization of classification, treatment and outcomes of acral melanoma (AM) patients. The AM genetic landscape differs in vital ways from that of other cutaneous melanoma (CM). These differences have important implications in understanding pathogenesis, treatment and prognosis. The selection of molecularly targeted therapy must be adapted for AM. It is also critical to recognize that tumor development is far more complex than an isolated event, reliably treated by a medication acting on a single target. Tumors exhibit intratumor genetic heterogeneity, metastasis may have different genetic or epigenetic features to primary tumors and tumor resistance may develop due to the activation of alternative genetic pathways. Micro-environmental, immune and epigenetic events contribute and sustain tumors in complex ways. Treatment strategies with multiple targets are required to effectively disrupt the tumor ecosystem. This review attempts to translate the current molecular understanding of AM into digestible concepts relevant to the practice of dermatology. The focus is tumor genetics defining potentially treatable cancer pathways, contextualised within the relevant pathological and molecular features.