BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for Cutaneous Malignant Melanoma


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 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 patient; and (3) early age (< 50 years old) of onset. A positive family history of melanoma is the most significant risk factor. An example of a commercially available genetic test is Melaris®, manufactured by Myriad®.

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.




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


American Academy of Dermatology (2011) Guidelines of care for the management of primary cutaneous melanoma. Journal of the American Academy of Dermatology, Vol. 65, No. 5, 1032-1047.

BlueCross BlueShield Association. Medical Policy Reference Manual. (3:2017). Genetic testing for familial cutaneous malignant melanoma (2.04.44). Retrieved July 26, 2017 from BlueWeb. (35 articles and/or guidelines reviewed)

Carlson, J., Caldeira, X., Tarasen, A., Sheehan, C., Otto, G., Miller, V., et. al., (2017, January) 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.

Helgadottir, H., Höiom, V., Tuominen, R., Nielsen, K., Jönsson, G., Olsson, H., et. al. (2016, June) 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, April) 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 Cancer Institute (2015). Genetics of Skin Cancer (PDQ®) - for health professionals. Retrieved September 28, 2015 from: 

National Comprehensive Cancer Network (2016, November) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Melanoma. Retrieved July 26, 2017 from

National Government Services, Inc. (2016, April) Local Coverage Determination (LCD): Molecular Pathology Procedures (L35000), Retrieved January 1, 2017 from

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.

Winifred S. Hayes, Inc. Genetic Test Evaluation Overview. (2010, June; last update search June 2014). CDKN2A testing for malignant melanoma. Retrieved September 25, 2015 from (162 articles and/or guidelines)

Yang, X., Pfeiffer, R., Wheeler, W., Yeager, M., Chanock, S., Tucker, M., et al. (2009). Identification of modifier genes for cutaneous malignant melanoma in melanoma-prone families with and without CDKN2A mutations. International Journal of Cancer, 125 (12), 2912 - 2917. (Level 4 evidence - Independent)




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