What is Skin Cancer (Melanoma)?
Melanoma is a type of skin cancer that occurs when melanocytes grow and multiply uncontrollably. Melanocytes are cells responsible for producing the pigment that gives skin its color. Melanoma can originate from pigmented lesions on the skin (commonly known as “moles”) or may present as completely new formations starting from as small as 1–2 mm and in various colors. If the number of moles or pigmented skin lesions on the body is high (more than 25), any changes in these should be monitored more closely. Moreover, in conditions such as Xeroderma Pigmentosum—a DNA repair disorder—or in individuals who have previously had melanoma, the risk of developing melanoma increases significantly, especially with sun exposure.
Melanoma most commonly occurs on the skin. However, it can also be found, though more rarely, in the eyes or mucosal surfaces.
What is Genetic Testing for Skin Cancer (Melanoma)?
All melanomas arise due to genetic variants. (Loss of cell division control is caused by genetic alterations, most of which are somatic.) However, about 5–10% of all malignant melanomas are familial. This means individuals carry a mutation in a gene associated with melanoma that was inherited from a parent, and they have a 50% chance of passing this gene on to their children. It is important to note that not everyone who carries these mutations will necessarily develop cancer. However, individuals with these mutations may develop cancer during their lifetime with a probability of 60–90%. These susceptibility genes are also known to cause the development of multiple pigmented atypical nevi.
One of the best-known genes associated with familial melanoma is CDKN2A. However, in recent years, an increasing number of genes—such as MC1R, MITF, CDK4, POT1, TERT, ACD, TERF2IP, and BAP1—have been shown to be linked to familial melanoma. These genes are also known to increase the risk for other cancers, especially pancreatic cancer, alongside recurrent melanomas. In such cancers, it is understood that multiple low-impact variants across different genes and environmental factors play a combined role—known as multifactorial inheritance. Therefore, assessing risk in families becomes more challenging.
While there are guidelines indicating when to perform genetic testing—considering the geographical region of high risk, number of melanoma cases in the family, age at onset, and presence of other malignancies in the family—the most accurate approach is for individuals with a family history of melanoma to consult a qualified healthcare professional without delay.
As with all cancers, early diagnosis is crucial.
Genetic Testing for Skin Cancer is Usually Performed for the Following Purposes:
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Risk Assessment: To evaluate a person's risk of developing melanoma, especially by taking into account family history and personal risk factors.
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Genetic Mutation Detection: Some genetic mutations increase the risk of melanoma. This test is performed to identify such mutations.
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Treatment Planning: Results from melanoma genetic testing can influence treatment planning. Especially new treatment options like immunotherapy or targeted therapies may be considered.
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Family Counseling: Test results may also affect the risk assessments of family members. Thus, other individuals in the family can be evaluated for their risk.
Familial Susceptibility Screening Panel
Hereditary Cancer Screening Panel: This panel includes around 220 genes known to be associated with various cancers and approximately 400 candidate genes suspected to be cancer-related. As new cancer genes are identified, they are added to the panel to keep it up to date.
Genetic Tests from Tissue for Skin Cancer That Help Determine Treatment Options:
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BRAF (V600E, V600K)
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KRAS
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NRAS
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HRAS
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EGFR
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ALK (FISH)
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MET (FISH)
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KIT sequencing analysis
