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.
The clinical utility of genetic testing for hereditary melanoma families is debatable because CDKN2A status may not impact medical management in patients with melanoma.
Germline CDKN2A mutations affecting p16(INK4a) were detected in 8 unrelated probands (13.6 %), including 7 familial cases and one patient with multiple melanomas; 4 out of 8 mutation carriers met the criteria for familial melanoma and had multiple primary lesions.
A small proportion of melanoma cases can be ascribed to the presence of highly penetrant germline mutations, and approximately 40% of hereditary melanoma cases are caused by CDKN2A mutations.
We compared the gene expression profile of SFs from FM individuals with two distinct CDKN2A/p16 mutations (V126D-p16 and R87P-p16) with the gene expression profile of SFs from age-matched individuals without p16 mutations and with no family history of melanoma.
Little is known about the impact of knowledge of CDKN2A and MC1R genotype on melanoma prevention behaviors like sun avoidance and skin examination in the context of familial melanoma.
Germline mutations in the CDKN2A locus, encoding the key tumor suppressor proteins p16/INK4A and p14/ARF, are frequently present in kindreds with hereditary cutaneous melanoma but have seldom been reported in families with genetic susceptibility to head and neck squamous cell carcinomas (HNSCC).
Exposure to ultraviolet radiation (UVR) and the familial melanoma susceptibility gene p16 (CDKN2A) are among the major risk factors which have been identified to contribute to the development of melanoma, and also significantly contribute to squamous cell carcinoma.