Melanoma is the most deadly of the common
skin cancers and its incidence is rapidly increasing. Approximately 10% of cases occur in a familial context. To date,
cyclin-dependent kinase inhibitor 2A (CDKN2A), which was identified as the first
melanoma susceptibility gene more than 20 years ago, is the main high-risk gene for
melanoma. A few years later
cyclin-dependent kinase 4 (CDK4) was also identified as a
melanoma susceptibility gene. The technologic advances have allowed the identification of new genes involved in
melanoma susceptibility:
Breast cancer 1 (BRCA1) associated
protein 1 (BAP1), CXC genes,
telomerase reverse transcriptase (TERT), protection of telomeres 1 (POT1), ACD and TERF2IP, the latter four being involved in telomere maintenance. Furthermore variants in
melanocortin 1 receptor (MC1R) and
microphthalmia-associated transcription factor (MITF) give a moderately increased risk to develop
melanoma.
Melanoma genetic counseling is offered to families in order to better understand the disease and the
genetic susceptibility of developing it. Genetic counseling often implies genetic testing, although patients can benefit from genetic counseling even when they do not fulfill the criteria for these tests. Genetic testing for
melanoma predisposition mutations can be used in clinical practice under adequate selection criteria and giving a valid test interpretation and genetic counseling to the individual.