Melanoma Predisposition (CDKN2A)

Clinical Features

Melanoma is a malignant tumor that originates in melanocytes, a specialized cell type that produces melanin pigments that determine skin, hair, and eye color (Lin and Fisher., PubMed ID: 17314970). Over the past few decades there has been a rise in the incidence of melanoma due to both improved awareness leading to additional diagnoses and to lifestyle changes that have resulted in an increase in sun exposure (Mehnert and Kluger., PubMed ID: 22723080). Most melanomas occur as sporadic cases with no recognized familial component; however, melanoma has been reported to be twice as common in persons with an affected parent, three times as common if a sibling is affected, and nine times as common if both a parent and a sibling are affected (Hemminki et al., PubMed ID: 12542525). Familial clustering is likely the result of genetic and environmental factors. Heritable alleles for melanoma susceptibility range from high-risk, high-penetrance alleles that are rare to low-risk, low-penetrance alleles that are common (Nelson et al., PubMed ID: 19095153). Mutations in the highly penetrant gene CDKN2A, and less frequently the CDK4 gene, are responsible for the majority of predisposition to melanoma cases. Individuals with genetic predisposition to melanoma have an earlier age of onset. For example, the median age at melanoma diagnosis is significantly lower in carriers of CDKN2A mutations (36 years) than in patients from families with wildtype CDKN2A (45 years) (Goldstein et al., PubMed ID: 17047042). A family history of melanoma and pancreatic cancer may also suggest inherited mutations in CDKN2A (Goldstein et al., PubMed ID: 10861313).


Survival of patients with malignant melanoma is directly related to early detection, screening, and early diagnoses, as well as UV avoidance (Rigel and Carucci, PubMed ID: 10986965).

Screening and Early Detection

Melanoma is a tumor with aggressive metastatic potential; however, if it is diagnosed while it is less than 1 mm, patients have a 94% survival rate as compared to after it grows to 3mm, when there is a less than 50% survival rate (Rigel and Carucci, PubMed ID: 10986965). Early, regular screening and detection can help a melanoma predisposed patient treat their tumor before it grows to become fatal. Melanoma confined to the epidermis carries no risk of death, making diagnosis before metastasis crucial (Austoker, J., BMJ. 1994; 308: 1642). Surgical excision proves to be nearly 100% successful in tumors caught early. This is critical because tumors discovered late and treated with chemotherapeutic methods have never generated response rates greater than 25% (Rigel and Carucci, PubMed ID: 10986965).

CDKN2A mutations have been linked to other cancers as well such as pancreatic carcinoma, multiple myeloma, breast cancer, head and neck cancer, respiratory malignancies, and laryngeal cancer (Debniak et al., PubMed ID: 16395703). Molecular confirmation and awareness of other cancer risks can lead to cancer screening and early diagnosis which improves patient outcomes (Dilworth et al., Journal of the American Society of Hematology. 2000; 95(5): 1869-1871).

UV Avoidance

Studies have proven a direct correlation between UV exposure and the risk of melanoma (Abbasi et al., PubMed ID: 15585738). Modification of sun exposure and increased sunscreen use are both methods patients should use to decrease their risk of melanoma (Austoker, J., BMJ. 1994; 308: 1642). Studies show that in countries where more sunscreen is used, melanoma incidence and mortality rates fall (Rigel and Carucci, PubMed ID: 10986965).

For more information on CDKN2A testing, please see our full Test Description.


This article is a summary of information that has been reported in the biomedical research literature. It is not medical advice for patients. All disease treatments should be under the direction of a qualified healthcare provider.

Last Updated: 9/22/2017