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Guiding Melanoma Risk Assessment


May is Skin Cancer Awareness Month

Did you know that 5-10% of melanomas are familial?

Even though melanomas account for only 1% of skin cancers, an estimated 99.780 people will develop one this year.1 And while ultraviolet (UV) light exposure, be it from the sun or a tanning bed, is one of the most common risk factors for this aggressive form of skin cancer, family history can also play a role.

Patients with familial melanoma inherit gene mutations that increase their risk of developing melanoma. Natera offers genetic testing for melanoma-predisposing genes as part of its Empower Hereditary Cancer Test. This Skin Cancer Awareness Month, we highlight the genes that predispose individuals to familial melanoma.

“Inheriting” Melanoma

Melanomas are considered familial if they occur in at least two first-degree relatives or at least three relatives on the same side of the family. Familial melanomas manifest when individuals inherit melanoma-predisposing gene mutations. These mutations are outlined below from Rossi and colleagues’ more in-depth review2.

The tumor suppressor gene CDKN2A was the first melanoma-predisposing gene identified. CDKN2A mutations are found in 20-40% of high-risk families, where they impair cell cycle arrest2.

CDK4 was discovered second, and its prevalence is far less than that of CDKN2A. Mutations in either CDKN2A or CDK4 cause a hereditary cancer syndrome known as Familial atypical multiple mole-melanoma (FAMMM). In addition to melanoma, individuals with FAMMM are at increased risk to develop pancreatic cancer.

Mutations in BAP1 can also predispose individuals to melanoma. Not only that, BAP1 mutations can predispose individuals to a wide variety of cancers, including those of the eye (uveal melanoma), mesothelium (mesothelioma), skin (basal cell carcinoma), and kidneys (renal cell carcinoma). In fact, there is a name for this heritable condition: BAP1 tumor predisposition syndrome.3

Next-generation sequencing enabled the discovery of MITF (microphthalmia-associated transcription factor). A single mutation in MITF can predispose individuals to melanoma by promoting the survival and proliferation of skin cells.

Guiding Melanoma Risk Assessment

The Empower Hereditary Cancer Test can be used to test for the multiple melanoma-predisposing genes. For example, Empower can test for CDKN2A, CDK4, BAP1, and MITF as part of its 40-gene multi-cancer panel, which spans actionable hereditary cancer genes across 8 major organ systems.

As an integral component of the genetic testing journey, genetic counseling is recommended for patients seeking genetic testing.4 To help patients better understand what genetic testing means for them, Natera offers pre- and post-test genetic information sessions via its board-certified genetic counselors.

Natera is committed to making high-quality hereditary cancer testing accessible for you and your patients. If you have questions about cost, please call the Natera billing phone number at 1-844-384-2996 (8 am-7 pm CT M-F), or visit the Natera billing page. Please do not call the Natera billing phone number for questions about genetic counseling. You can schedule a complimentary information session with a board-certified genetic counselor here.

Visit here to learn more about melanoma prevention and early screening :


1Melanoma of the skin.!/cancer-site/Melanoma%20of%20the%20skin

2Rossi M, et al. Familial Melanoma: Diagnostic and Management Implications. Dermatol Pract Concept. 2019;9(1):10-16.

3Pilarski R, et al. BAP1 Tumor Predisposition Syndrome. 2016 Oct 13 [Updated 2020 Sep 17]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from:

4Genetic Counseling and Testing for People at High Risk of Melanoma. August 2019.