Approximately ten percent of all melanoma cases are hereditary. Individuals with certian mutations face up to a 76% risk of developing melanoma. MELARIS assesses a persons risk of developing melanoma. This test detects inherited mutations in the p16 gene (also called CDKN2A or INK4A), which occur in up to 40% of families with hereditary melanoma.
The clinical validity is related to the interpretation of the results of the genetic analysis for the individual patient. One issue common to genetic testing for any type of cancer susceptibility is determining the clinical significance of individual mutations. For example, mutations in the CDKN2A gene can occur along its entire length and some of these mutations represent harmless polymorphisms or noncoding mutations. Interpretation will improve as more data accumulates regarding the clinical significance of individual mutations in families with a known hereditary pattern of melanoma. However, the penetrance of a given mutation will also affect its clinical significance, particularly since the penetrance of CDKN2A mutations may vary with ethnicity and geographic location.
If an affected individual tests positive for a CDKN2A mutation, he/she may be at increased risk for a second primary melanoma compared to the general population. However, it is unclear how a positive test result would alter patient management as limited and protected sun exposure and increased surveillance would be recommended to any patient with a malignant melanoma, regardless of the presence of a CDKN2A mutation, On the other hand, a positive result will establish a mutation, thus permitting targeted testing for the rest of the family. Additionally, a positive mutation in an affected family member increases the likelihood of its clinical significance if detected in another family member. A negative test is not interpretable.
The Melanoma Genetics Consortium, comprised of familial melanoma researchers worldwide, published a recommendation that genetic testing for melanoma susceptibility should not be offered outside of a research setting. They stated, “Until further data become available, however, clinical evaluation of risk remains the gold standard for preventing melanoma. First-degree relatives of individuals at high risk should be engaged in the same programmes of melanoma prevention and surveillance irrespective of the results of any genetic testing.”
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