Clinicopathological characteristics and mutation profiling in primary cutaneous melanoma

Am J Dermatopathol. 2015 May;37(5):389-97. doi: 10.1097/DAD.0000000000000241.


Background: The incidence of mutations in malignant melanoma varies remarkably according to the subtype of melanoma, and this in itself is affected by racial and geographical factors. Studies screening melanoma case series for different types of mutations are relatively rare.

Method: The authors analyzed the frequency of various somatic point mutations of 10 genes in 106 primary cutaneous melanoma cases. The mutations (BRAF, NRAS, KIT, CDKN2A, KRAS, HRAS, PIK3CA, STK11, GNAQ, CTNNB1) were evaluated with real-time PCR-based PCR-Array through allele-specific amplification, and the results were correlated with various clinicopathological characteristics.

Results: Mutations were found in 64.2% of the melanomas overall. BRAF (42.5%), NRAS (15.1%), and CDKN2A (13.2%) were the 3 most common mutations. BRAF and NRAS mutations were more frequent in nodular and superficial spreading melanomas (P < 0.001). Associations with BRAF mutation were as follows: male gender [odds ratio (OR) = 2.4], younger age (OR = 2.7), superficial spreading (OR = 15.6) and nodular melanoma (OR = 9.5), trunk localization (OR = 6.3), and intermittent sun exposure (OR = 4.6). A considerable percentage of V600K (44.4%) mutations were found among the BRAF mutations, whereas KIT mutations (3.8%) were less frequent. Multiple mutations were detected in 13.2% of the melanomas. The most common co-occurrences were in the BRAF, NRAS, and CDKN2A genes.

Conclusions: The authors analyzed 10 somatic mutations in the main subtypes of primary cutaneous melanomas from the western region of Turkey. Mutations were found in 64.2% of the melanomas overall. The most common mutations were in the BRAF and NRAS genes. In addition to other less common mutations, a notable number of multiple mutations were encountered. The multiplicity and concurrence of mutations in this study may provide further study areas for personalized targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Chi-Square Distribution
  • DNA Mutational Analysis* / methods
  • Female
  • GTP Phosphohydrolases / genetics
  • Gene Frequency
  • Genes, p16
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • Membrane Proteins / genetics
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Point Mutation*
  • Predictive Value of Tests
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-kit / genetics
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Turkey
  • Young Adult


  • Biomarkers, Tumor
  • Membrane Proteins
  • Proto-Oncogene Proteins c-kit
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human