Update in molecular diagnostics in melanocytic neoplasms

Adv Anat Pathol. 2012 Nov;19(6):410-6. doi: 10.1097/PAP.0b013e318271a5cb.


Future classification systems for melanocytic neoplasms will likely include the integration of molecular aberrations. A number of studies have shown that many gene mutations and chromosomal copy number aberrations may correlate with characteristic clinical and morphologic features for melanocytic neoplasms. This review discusses newly described familial germline mutations such as the BRCA1-associated protein-1 familial melanoma syndrome, recently described somatic mutations, and chromosomal copy number aberrations recently described in melanoma. Further, we discuss how these specific molecular aberrations correlate with specific clinical and morphologic features in melanocytic neoplasm and their implications for prognosis and molecular diagnostics. In addition, we discuss state of the art advancements in molecular diagnostics for melanocytic neoplasms and newly developed fluorescence in situ hybridization assays including the utility of fluorescence in situ hybridization for 9p21 in spitzoid melanocytic neoplasms. Lastly, we discuss a phenomenon known as paradoxical activation of wild-type BRAF seen in patients treated with vemurafenib and some potential clinical presentations of this process.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 9 / genetics
  • Dysplastic Nevus Syndrome / diagnosis*
  • Dysplastic Nevus Syndrome / genetics
  • Germ-Line Mutation
  • Humans
  • In Situ Hybridization, Fluorescence
  • Indoles / adverse effects
  • Melanoma / diagnosis*
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Molecular Diagnostic Techniques*
  • Nevus, Epithelioid and Spindle Cell / diagnosis
  • Nevus, Epithelioid and Spindle Cell / genetics
  • Prognosis
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics
  • Sulfonamides / adverse effects
  • Transcriptional Activation / drug effects
  • Ubiquitin-Protein Ligases / genetics*
  • Vemurafenib


  • Antineoplastic Agents
  • Indoles
  • Sulfonamides
  • Vemurafenib
  • BRAP protein, human
  • Ubiquitin-Protein Ligases