Influence of germline genetic variants on dermoscopic features of melanoma

Abstract

Nevus count is highly determined by inherited variants and has been associated with the origin of melanoma. De novo melanomas (DNMMs) are more prevalent in patients with a low nevus count and have distinctive dermoscopic features than nevus‐associated melanomas. We evaluated the impact of nine single nucleotide polymorphisms (SNPs) of MTAP (rs10811629, rs2218220, rs7023329 and rs751173), PLA2G6 (rs132985 and rs2284063), IRF4 (rs12203592), and PAX3 (rs10180903 and rs7600206) genes associated with nevus count and melanoma susceptibility, and the MC1R variants on dermoscopic features of 371 melanomas from 310 patients. All MTAP variants associated with a low nevus count were associated with regression structures (peppering and mixed regression), blue‐whitish veil, shiny white structures, and pigment network. SNPs of PLA2G6 (rs132985), PAX3 (rs7600206), and IRF4 (rs12203592) genes were also associated with either shiny white structures or mixed regression (all corrected p‐values ≤ .06). Melanomas from red hair color MC1R variants carriers showed lower total dermoscopy score (p‐value = .015) and less blotches than melanomas from non‐carriers (p‐value = .048). Our results provide evidence that germline variants protective for melanoma risk and/or associated with a low nevus count are associated with certain dermoscopic features, more characteristic of de novo and worse prognosis melanomas.

Multiple primary melanomas: Is there a correlation between dermoscopic features and germline mutations?

“…RHC MC1R variants were reported to influence CM features, reducing the pigmentation and the development of dermoscopic structures, including a lower number of blotches, due to the reduced synthesis of eumelanin. Non‐carriers of RHC variants were shown to have darker shades of colours, asymmetry and more structures 6 . Specific genetic variants in MTAP (allele rs10811629_G, rs2218220_T and rs7023329_G) were correlated with regression structures (peppering, mixed regression), blue‐whitish veil, shiny white structures and pigment network, while others in PAX3 (allele rs132985_T), PLA2G6 (rs7600206_C), IRF4 (rs12203592_T) with shiny white structures or mixed regression 6 …”

“…Currently, a possible association between germline mutations and dermoscopic features has been proposed 5,6 . Structureless areas are often detected in case of CDKN2A mutations with a couple of variants of MC1R of the RHC type and streaks/pigmented networks in their absence.…”

“…Structureless areas are often detected in case of CDKN2A mutations with a couple of variants of MC1R of the RHC type and streaks/pigmented networks in their absence. MITF ‐mutated subjects may show a nonspecific pattern (amelanotic/hypomelanotic nodular CM) with atypical polymorphic vessels 6,7 . RHC MC1R variants were reported to influence CM features, reducing the pigmentation and the development of dermoscopic structures, including a lower number of blotches, due to the reduced synthesis of eumelanin.…”

On Naevi and Melanomas: Two Sides of the Same Coin?

“…The different alleles exhibit differential expression levels that also influence a range of key immunomodulatory molecules and cytokines, and melanocyte growth and survival after UV exposure (59). Research continues on untangling which of these many effects contribute to nevus and/or melanoma formation and behavior (43,60).…”