Melanoma: a genetics guide for surgeons

Melanoma is considered the most lethal cutaneous malignancy when not detected early and treated at early stages. Whilst up to 90% of new melanoma diagnoses are attributable to excess ultraviolet radiation, genetic predisposition plays a pivotal role in melanomagenesis, making it imperative for surgeons, at the forefront of melanoma diagnosis and management, to thoroughly grasp this concept. Identification of genetically high-risk patients enables targeted surveillance, earlier diagnosis, and timely intervention, reducing melanoma-related morbidity and mortality despite the complexity of the underlying genetic landscape. However, in recent years, there have been several pathogenic variants identified that increase the risk of melanoma development. These pathogenic variants also contribute to the development of other cancers, constituting several cancer syndromes. As such, it is becoming increasingly important for surgeons to appreciate the fundamentals of genetic predisposition and to also consider non-melanomatous cancers in their practice. This article aims to outline the contribution of various pathogenic variants to the development of melanoma and other cancers, and in turn, how carriers of these variants should be managed, whilst highlighting the indications for genetic screening for some variants. Melanoma-dominant syndromes, such as CDKN2A , CDK4 , and POT1 , and melanoma-subordinate syndromes are described herein. Knowledge of these conditions will enable surgeons to incorporate these genetic insights into clinical practice and offer more personalised and effective care to patients with melanoma.