From this cohort, we selected 106 MUT<sup>+</sup> patients (with familial melanoma or apparently sporadic melanoma) and 199 CDKN2A germline mutation-negative (MUT<sup>-</sup>) patients with sporadic melanoma who were matched by age and sex and had a similar tumor stage distribution.
We conclude that multigene panel testing for familial melanoma is appropriate considering the additional 4% diagnostic yield in non-CDKN2A/CDK4 families.
MC1R variants decreased the age at diagnosis in all groups and were associated with an increased prevalence of SCC, especially in patients with familial melanoma without CDKN2A mutations.
The presence of germline <italic>CDKN2A/B</italic> inactivation together with the presence of multiple anatomically, histologically, and genetically distinct astrocytic neoplasms, both with accompanying somatic loss of heterozygosity for the <italic>CDKN2A/B</italic> deletion, led to a diagnosis of familial melanoma-astrocytoma syndrome.
We carried out a mutational analysis of CDKN2A, CDK4 exon 2, POT1 p.S270N, MITF exon 10, MC1R, and the TERT promoter in 106 high-risk patients with familial melanoma (FM) and sporadic multiple primary melanoma (spMPM) from Central Italy and evaluated mutations according to the clinicopathological characteristics of patients and lesions.
Kaplan Meier and Cox proportional hazards regression models were used to assess survival in CDKN2A(mut) (n = 96) and CDKN2A(wt) (n = 377) familial melanoma cases and in matched sporadic melanoma cases (n = 1042).All statistical tests were two-sided.
Rare CDKN2A loss-of-function mutations are a cause of familial melanoma and offer the opportunity to determine the impact of CDKN2A haploinsufficiency on glucose homeostasis in humans.