Germline Variants in Childhood Cutaneous Melanoma

Exposure to UVR and genetic variation associated with fair skin and the development of melanocytic nevi are the major risk factors for cutaneous melanoma (CM) ( Landi et al., 2020 ; Whiteman and Green, 1994 ). High-penetrance pathogenic variants associated with CM have been identified in several genes ( Abdel-Rahman et al., 2011 ; Aoude et al., 2015b ; Horn et al., 2013 ; Hussussian et al., 1994 ; Njauw et al., 2012 ; Robles-Espinoza et al., 2014 ; Zuo et al., 1996 ). Screening studies have estimated that 2–5% of patients with CM have a predisposing variant in one of the major high-penetrance genes: CDKN2A, CDK4, BAP1, and POT1 ( Aitken et al., 1999 ; Aoude et al., 2015a ; Begg et al., 2005 ; Simonin-Wilmer et al., 2022 ), leading to clusters of cases in families.