BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for Cutaneous Malignant Melanoma

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018


Cutaneous melanoma is the third most common type of skin cancer, but the most lethal. Some cases of cutaneous malignant melanoma (CMM) are familial. Potential genetic markers for this disease are being evaluated in affected individuals with a family history of the disease and in unaffected individuals in a high risk family.

A genetic predisposition to cutaneous malignant melanoma is suspected in specific clinical situations: (1) melanoma has been diagnosed in multiple family members; (2) multiple primary melanomas have been identified in a single individual; and (3) early age of onset (< 50 years old). A positive family history of melanoma is the most significant risk factor and is estimated at approximately 10% of melanoma cases.

The two main genetic variants linked to familial cutaneous malignant melanoma susceptibility are CDKN2A (also called p16 or INK4A) and CDK4. However, studies have indicated that the clinical sensitivity of genetic testing for variances associated with familial CMM is difficult to ascertain due to differences in gene penetrance, variant interpretation, study populations, sun exposure, and preventative measures. While familial variants associated with increased risk for developing melanoma have been identified, changes in clinical management and improved health outcomes as a result of genetic testing for asymptomatic individuals is uncertain. Examples of commercially available tests include: Melaris®.




Well-designed studies in peer-reviewed journals, which evaluate genetic testing for variants associated with susceptibility to cutaneous malignant melanoma, are lacking.


American Academy of Dermatology (2011). Guidelines of care for the management of primary cutaneous melanoma. Retrieved July 12, 2018 from

BlueCross BlueShield Association. Medical Policy Reference Manual. (3:2018). Genetic testing for familial cutaneous malignant melanoma (2.04.44). Retrieved July 12, 2018 from BlueWeb. (35 articles and/or guidelines reviewed)

Carlson, J., Caldeira, X., Tarasen, A., Sheehan, C., Otto, G., Miller, V., et al. (2017). Next-generation sequencing reveals pathway activations and new routes to targeted therapies in cutaneous metastatic melanoma. American Journal of Dermatopathology, 39 (1), 1-13. Abstract retrieved July 26, 2017 from PubMed database.

DiLorenzo, S., Fanale, D., Corradino, B., Calo, V., Rinaldo, G., Bazan, V., et al. (2016). Absence of germline CDKN2A mutation in Sicilian patients with familial malignant melanoma: could it be a population-specific genetic signature? Cancer Biology & Therapy, 17 (1), 83-90. (Level 3 evidence)

Helgadottir, H., Höiom, V., Tuominen, R., Nielsen, K., Jönsson, G., Olsson, H., et al. (2016). Germline CDKN2A mutation status and survival in familial melanoma cases. Journal of the National Cancer Institute, 108 (11). Abstract retrieved July 26, 2017 from PubMed database.

Melamed, R., Aydin, I., Rajan, G., Phelps, R., Silvers, D., Emmett, K., et al. (2017). Genomic characterization of dysplastic nevi unveils implications for diagnosis of melanoma. Journal of Investigational Dermatology, 137 (4), 905-909. Abstract retrieved July 27, 2017 from PubMed database.

National Comprehensive Cancer Network. (2018). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Melanoma. Retrieved July 12, 2018 from the National Comprehensive Cancer Network.

Soura, E., Eliades, P. J., Shannon, K., Stratigos, A. J., & Tsao, J. (2016). Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome. Journal of the American Academy of Dermatology, 74 (3), 395-407. Abstract retrieved August 11, 2016 from PubMed database.




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