Melanoma is one of the most serious types of skin cancer. It begins when healthy color-producing cells called melanocytes change and grow out of control, eventually forming a mass called a tumor. Sometimes, melanoma develops from a normal mole a person already has on their skin. Melanoma can occur anywhere on the body.

Highly penetrant genes are responsible for approximately 45% of familial melanoma cases, with the remainder likely influenced by lower penetrant genes and environmental or other risk factors . Patients identified with a hereditary melanoma syndrome can benefit from increased surveillance and preventative steps to better manage their risk for cancer. Information obtained from candidate gene testing may potentially be helpful in guiding clinical management in the future. Also, if an inherited susceptibility is found, your patient’s family members can be tested to help define their risk. If a pathogenic variant is identified in your patient, close relatives (children, siblings, parents) could have as high as a 50% risk to also be at increased risk. In some cases, screening should begin in childhood.

The deepest layer of the epidermis, located just above the dermis, contains cells called melanocytes. Melanocytes produce the skin’s pigment or color. Melanoma begins when healthy melanocytes change and grow out of control, forming a cancerous tumor. A cancerous tumor is malignant, meaning it can grow and spread to other parts of the body. Sometimes, melanoma develops from a normal mole a person already has on their skin. When this happens, the mole will undergo changes that usually can be seen, such as changes in shape, size, color, or the border of the mole 

When found early, melanoma can often be cured with surgery. However, melanoma is 1 of the most serious forms of skin cancer. It can grow deep into the skin, called invasive melanoma. It can also invade lymph nodes and blood vessels and spread to distant parts of the body, called metastatic melanoma.

The most common cause for HM are mutations in the gene CDKNA. Changes in this gene are found in approximately 20-40% of families with multiple people with melanoma, and are inherited in a dominant way. Individuals with a CDKNA mutation also have a higher risk for pancreatic cancer and may have a greater number of atypical moles. Besides CDKNA, there are other cancer-risk genes associated with HM and each one leads to a different set of cancer risks.

Specific genetic changes, or mutations, in melanoma can involve the BRAF, NRAS, NF-1, or KIT genes. BRAF mutations are found in about 50% of melanomas

The skin protects against infection and injury, helps regulate body temperature, stores water and fat, and produces vitamin D. Skin is made up of the epidermis (outer layer), the dermis (inner layer), and the hypodermis (deep layer of fat). The deepest layer of the epidermis contains melanocytes

 Hereditary melanoma syndromes are conditions that impact other areas of an individual’s body in addition to increasing their risk for melanoma. A syndrome can be inherited in a dominant, de novo, or recessive manner. Some examples of hereditary melanoma syndromes are listed below:

Cowden syndrome (CS)

People with Cowden syndrome often have large heads (macrocephaly) and are at an increased risk for different types of benign and malignant tumors, including melanoma, and endometrial, thyroid, and breast cancer. CS is caused by a mutation in the PTEN gene. CS increases the risk for melanoma to at least 5%. The lifetime risk for endometrial cancer for a woman with Cowden syndrome is around 28%, while their risk for breast cancer can be as high as 85%.

Li-Fraumeni syndrome (LFS)

 Li-Fraumeni syndrome is caused by a mutation in the TP53 gene. People with LFS have up to a 78% lifetime risk for cancer. Many different types of cancer can occur in LFS, and more than one kind can arise in a single person. The risk for melanoma is also increased. It is important to diagnose LFS, because exposure to radiation therapy raises the cancer risk even further.

Melanoma is the fifth most common cancer among men and the sixth most common cancer among women.  

Melanoma is 20 times more common in white people than in black people. The average age of diagnosis is 65. Before age 50, more women are diagnosed with melanoma than men. However, by age 65, men are 2 times more likely to be diagnosed with melanoma. By age 80, men are 3 times more likely to be diagnosed with melanoma.  

The development of melanoma is more common as people grow older, but it also develops in younger people, including those younger than 30 years old. It is one of the most common cancers diagnosed in young adults, particularly for women. This year, about 2,400 cases of melanoma will be diagnosed in people age 15 to 29. 


A positive result means that a genetic mutation causing an increased risk for melanoma was identified. Your risk for other cancers or health conditions may also be increased, depending on the gene involved. Your doctor can use this information to customize your care, which could include increased screening, preventative surgery, medication, and other steps. A positive result is also important for your family. Your parents, siblings, and children could have as high as a 50% chance to also have the mutation. As a result, sharing your genetic testing results with your relatives is important for their health.


A negative result indicates that a genetic mutation was not identified. A negative result may indicate that there is not a cancer-risk gene mutation in you or your family. However, it can also mean that the gene increasing risk in you or your family was not included on the ordered test, or even that it may not be currently known. Your doctor can use a negative result to continue your treatment and screening based on your clinical and family history, or they may consider another type of genetic testing.


 The third possible test result is called a Variant of Uncertain Clinical Significance. A gene variant is a genetic difference that could be disease-causing (mutation) or could be a normal finding (benign). More research is needed to determine whether the variant is important or not, and it should be treated as a negative result until more information is available.

Sun exposure. Exposure to ultraviolet (UV) radiation from the sun plays a major role in the development of skin cancer.

Indoor tanning. People who use tanning beds, tanning parlors, or sun lamps have an increased risk of developing all types of skin cancer.

Family history. About 10% of people with melanoma have a family history of the disease. If a person has a close relative (parent, brother, sister, or child) who has been diagnosed with melanoma, his or her risk of developing melanoma is 2 to 3 times higher than the average risk.

Familial melanoma. Although changes, called mutations, in specific genes, such as CDKN2A, CDK4, P53, and MITF, have been identified that may lead to melanoma

Other inherited conditions People with specific inherited genetic conditions, including xeroderma pigmentosumretinoblastomaLi-Fraumeni syndrome, Werner syndrome, and certain hereditary breast and ovarian cancer syndromes, have an increased risk of developing melanoma.

Weakened or suppressed immune system. People who have weakened immune systems or use certain medications that suppress immune function have a higher risk of developing skin cancer, including melanoma