Update in molecular diagnostics in melanocytic neoplasms.
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.
Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Chelsea
C
Cooper
Jennifer
J
Sorrell
Pedram
P
Gerami
D000970:Antineoplastic Agents / Q000009:adverse effects; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004416:Dysplastic Nevus Syndrome / Q000175:diagnosis* / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007211:Indoles / Q000009:adverse effects; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D025202:Molecular Diagnostic Techniques; D018332:Nevus, Epithelioid and Spindle Cell / Q000175:diagnosis / Q000235:genetics; D011379:Prognosis; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D013449:Sulfonamides / Q000009:adverse effects; D015533:Transcriptional Activation / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000077484:Vemurafenib
D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases