Molecular Profile of Cutaneous Melanoma
Objectives: Сutаnеоus mеlаnоmа (CM) is characterized bу molecular heterogeneity. The aim of the study was to clarify clinical and pathological characteristics associated with gene mutations in the MAPK signaling pathway in Russian CM patients.
Methods: BRAF, NRAS, KIT, and PDGFRA mutations were evaluated in tumor DNA from 214 CM patients with Sanger sequencing of PCR products.
Results: Analysis of 173 non-acral CM revealed somatic mutations in BRAF (61.3%), NRAS (15.0%), KIT (1.1%), PDGFRA (1.1%), while 41 metastatic melanomas with unknown primary sites demonstrated a lower frequency of BRAF (46.3%) and NRAS (12.2%) mutations. The spectrum of BRAF and NRAS mutations differs among CM specimens, depending on tumor location and UV exposure. BRAFV600E was found in 90.4% of BRAF+ melanomas, that is, 52.8% of all CM cases, among them in 70% of patients aged under 30 years. KIT exon 11 mutations (p.V559A and p.Q556_W557del) were detected in CM, affecting the skin areas exposed to UV insolation (lower lip and shoulder). Somatic PDGFRA mutations (p.R558C and p.S847L) were found in patients with metastatic nodular CM of shin and back. Substitution c.2472C>T PDGFRA (silent mutation p.V824V or functional synonymous SNP rs2228230:C>T) was detected in CM cases with low expression of immunohistochemical diagnostic markers (poorly differentiated CM).
Conclusion: Molecular genetic study has revealed the prevalence of BRAF, NRAS and KIT (italics) gene mutations which were associated with primary non-acral CM location, whereas PDGFRA (italics) alterations were detected in a few metastatic poorly differentiated CM cases.
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