Asper Biogene – genetic testing company

Melanoma
NGS panel

Del/dup analysis

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Testing of individuals with family history of cutaneous malignant melanoma
3. Testing of at-risk family members for known mutations
4. Genetic counseling

Cutaneous malignant melanoma (CMM) is the third most common type of skin cancer and most common melanoma subtype accounting for more than 90% of cases worldwide. Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs mostly in skin but may also occur in noncutaneous sites such as eye, ear, urinary and gastrointestinal tract, leptomeninges, and oral and genital mucous membrane.

A significant risk factor for CMM is ultraviolet (UV) radiation. Thus, CMM is potentially preventable by diminishing exposure to UV radiation. However, other risk factors including numbers of naevi, eye and hair colour, freckles, familial history and genetic predisposition also play an important role in the risk of developing melanoma.

The most commonly applied clinical prediction rule is the ABCDE rule: Asymmetry, irregular Borders, more than one or uneven distribution of Colour, Diameter greater than 6 mm, and Evolution of moles. One third of CMMs appear from preexisting naevi (including both acquired and congenital types), whereas the rest appear to arise de novo. The presence of numerous melanocytic naevi (normal or atypical) confers the risk of CMM development.

Up to date, there are four major types of CMM: 1) the superficial spreading melanoma – 70% of CMMs; 2) the nodular melanoma – 15% to 30% of CMMs; 3) the lentigo maligna melanoma (or melanoma in situ) – less than 5% of CMMs; 4) the acral lentiginous variety – less than 5% of all CMMs, but accounts for 35% to 65% of CMMs diagnosed in dark-skinned individuals (African Americans, Asians, and Hispanics).

Light-skinned people have a 20 times greater risk of developing melanoma than dark-skinned people. The incidence of CMM in most developed countries has been steadily rising at least 4–6% per annum in recent decades. CMM accounting for 3% of all skin cancers, it results in 65% of all skin cancer deaths.

The test covers the most known genetic causes of CMM types.

The most cases of CMM are sporadic. A family history of CMM can be documented in 6% to 12% of new cases. Members of affected families share 50% cumulative lifetime risk of developing CMM. The familial CMM is inherited in an autosomal dominant pattern.

Incidence rate of CMM is 2.8–3.1 per 100,000 worldwide. There is a significant variation between countries, with the highest rate reported in Australia (37 per 100,000) and the lowest in South-Central Asia (0.2 per 100,000). In the United States, melanoma is the fifth most common cancer in men, affecting 30 in 100,000 men per year, and the sixth most common cancer in women, affecting 18 in 100,000 women per year. In Europe the incidence rate of CMM is lower compared with Australia and the United States, but within Europe incidence rates vary widely: Switzerland has the highest rates (19.2 per 100,000) and Greece the lowest rates (2.2 per 100,000).

References:
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Harrington E, Clyne B, Wesseling N, et al. Diagnosing malignant melanoma in ambulatory care: a systematic review of clinical prediction rules. BMJ Open. 2017;7(3):e014096. Published 2017 Mar 6. doi:10.1136/bmjopen-2016-014096. PMID: 28264830
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