Melanoma
NGS panel
Genes:
(full coding
region): |
BAP1, BRCA2, CDK4, CDKN2A, MC1R, MITF, POT1, PTEN, RB1, TERT, XRCC3
List of diseases covered by the panel |
| Lab method: |
NGS panel with CNV analysis |
| Specimen requirements: |
2-4 ml of blood with anticoagulant EDTA
1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker. |
Del/dup analysis
| Genes: |
CDK4, CDKN2A, CDKN2B, MITF |
| Specimen requirements: |
2-4 ml of blood with anticoagulant EDTA
1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker. |
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:
Ali Z, Yousaf N, Larkin J. Melanoma epidemiology, biology and prognosis. EJC Suppl. 2013;11(2):81-91. doi:10.1016/j.ejcsup.2013.07.012. PMID: 26217116
Badenas C, Aguilera P, Puig-Butillé JA, Carrera C, Malvehy J, Puig S. Genetic counseling in melanoma. Dermatol Ther. 2012;25(5):397-402. doi:10.1111/j.1529-8019.2012.01499.x. PMID: 23046018
Bashford MT, Kohlman W, Everett J, Parrott A, Pollin TI; Practice Guidelines Committee of the National Society of Genetic Counselors and the Professional Practice and Guidelines Committee of the American College of Medical Genetics and Genomics. Addendum: A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2019;21(12):2844. doi:10.1038/s41436-019-0586-y. PMID: 31332281
Cummins DL, Cummins JM, Pantle H, Silverman MA, Leonard AL, Chanmugam A. Cutaneous malignant melanoma. Mayo Clin Proc. 2006;81(4):500-507. doi:10.4065/81.4.500. PMID: 16610570
Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL; Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015;17(1):70-87. doi:10.1038/gim.2014.147. PMID: 25394175
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
Rigel DS, Friedman RJ, Kopf AW, Polsky D. ABCDE- an evolving concept in the early detection of melanoma. Arch Dermatol. 2005;141(8):1032-1034. doi:10.1001/archderm.141.8.1032. PMID: 16103334
Soura E, Eliades PJ, Shannon K, Stratigos AJ, Tsao H. Hereditary melanoma: Update on syndromes and management: Emerging melanoma cancer complexes and genetic counseling. J Am Acad Dermatol. 2016;74(3):411-422. doi:10.1016/j.jaad.2015.08.037. PMID: 26892651
