Update in Molecular Diagnostics in Melanocytic Neoplasms

*Department of Dermatology †Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Advances in anatomic pathology (Impact Factor: 3.23). 11/2012; 19(6):410-6. DOI: 10.1097/PAP.0b013e318271a5cb
Source: PubMed


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.

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    • "This is important, as the molecular alterations are associated with intracellular signaling pathway changes, clinical features, and responses to different treatment regimes. Molecular diagnosis could be included in the routine diagnosis for melanoma in the near future.103 More and more newly developed techniques are used in the molecular diagnosis of melanoma, such as tissue array, proteomics, and DNA sequencing.104 "
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    ABSTRACT: Fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH) are molecular techniques that have become valuable adjuncts in the diagnosis of histopathologically ambiguous melanocytic tumors. These techniques detect the presence of chromosomal gains or losses that are characteristic of malignant transformation in melanocytic neoplasms. CGH and FISH have been used to characterize distinct genomic characteristics of melanocytic tumors at various anatomic sites and tumors with certain histopathologic features (e.g. spitzoid, blue nevus-like, congenital nevi). Recent developments in this field include the transition of CGH from a research tool to a clinically available test and a new FISH probe set targeting chromosomal loci 11q13, 8q24, 6p25 and 9p21 that reportedly distinguishes melanoma from melanocytic nevi with a sensitivity and specificity of 94% and 98% respectively. Genomic analysis of melanocytic tumors also provides prognostic information. This review discusses these new advances in molecular diagnostics in melanoma and future directions in the field.
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