Germline mutations within the CDKN2A gene, coding for the cyclin-dependent kinase inhibitor p16, have been detected by screening in 8% of Swedish families with an inheritance of cutaneous melanoma (FMM) and dysplastic nevus syndrome (DNS).
Mutations in the cyclin-dependent kinase inhibitor-2A (CDKN2A) gene have been associated with a number of malignancies, most notably cutaneous malignant melanoma (CMM).
Evidence for comorbid OM and CM exists in patients with strong phenotypic expression of atypical nevi and conjunctival melanoma, although CDKN2A mutations have not been documented in patients with OM.
The current study sought to investigate whether the presence of germline CDKN2A mutations or the occurrence of cutaneous melanoma would result in constitutive genome-wide DNA methylation changes.
In this review we describe some of the important risk loci and their association to risk of developing cutaneous melanoma and also address the current clinical challenges in CDKN2A genetic testing.
The coexistence of ocular and cutaneous melanoma in some patients suggests a predisposition to both types and implicates mutations in the CDKN2A gene in a proportion of these cases.
Homozygous deletions of the CDKN2 locus were observed in 8 cases of cutaneous melanoma and 2 cases of uveal melanoma; mutations in CDKN2 exon 2 were found in 2 of the 46 cases with allelic deletion in 9p21.
Although mutations in two genes, CDKN2A and CDK4, have been shown to confer an increased risk of CMM, they account for only 20%-25% of families with multiple cases of CMM.
We performed a genome-wide scan of two Danish pedigrees with multiple cases of OMM (N = 10) and CMM (N = 3) and other malignancies (with no germline mutations in CDKN2A, CDK4, BRCA1, and BRCA2) to identify melanoma susceptibility genes.
This case report describes the first application of CDKN2A mutation analysis for discriminating a cutaneous melanoma metastasis from a new primary melanoma.
This is the first estimate of the contribution of BAP1 and CDK4 to a population-based sample of CMM and supports the previously reported estimate of CDKN2A germline mutation prevalence.