: Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma.
The GNN clustering was lower in families with increasing numbers of CMM (>/=3 cases) or presence of p16 mutations, the opposite being observed for LP and HDSE.
To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM.
Occurrence of ocular melanoma thirteen years after skin melanoma: two separate primaries or metastatic disease? A case solved with NRAS and CDKN2A (INK4A-ARF) mutational analysis.
We identified germline mutations in highly CM-associated genes (CDKN2A and CDK4) and low/medium-penetrance variants (MC1R and MITF) in patients with multiple primary CMs or individuals with one or more CM and a positive family history for CM or pancreatic cancer among first- or second-degree relatives.
To examine for the genetic basis of metastatic progression in cutaneous melanoma, we have compared loss of heterozygosity (LOH) of several selected chromosome regions that are implicated in the initiation and progression of melanoma, and alterations of the p16INK4a gene in 14 pairs of primary tumor and synchronous or asynchronous metastasis excised from the same patients.
Germ-line mutations in CDKN2A predispose to the familial atypical multiple-mole melanoma (FAMMM) syndrome but also have been seen in rare families in which only 1 or 2 individuals are affected by cutaneous malignant melanoma (CMM).
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.