A definite diagnosis cannot be established based on histologic features alone in a large number of Spitz nevi and spitzoid melanomas. In a vast majority of common benign and malignant melanocytic lesions, B-RAF and N-RAS mutations were described, but these were not detected in Spitz nevi. In contrast, H-RAS mutations were frequently encountered in Spitz nevi, but only rarely in melanomas. To date, B-RAF mutation analysis has not been reported in atypical Spitz nevi, and there are only a few reports of it in spitzoid melanomas. We analyzed 96 formalin-fixed, paraffin-embedded spitzoid melanocytic lesions for hotspot mutations in B-RAF, N-RAS, and H-RAS genes to test the assumption whether mutation analysis would assist a more accurate diagnosis of spitzoid melanocytic lesions, which are notoriously difficult to classify. B-RAF or N-RAS mutations were observed in 31 of 36 (86%) spitzoid melanomas, and in 6 of 7 (86%) spitzoid melanoma metastases. In contrast, none of the 14 Spitz nevi and none of the 16 atypical Spitz nevi had mutations in any of the three genes. A B-RAF or N-RAS mutation was found in 8 of 23 (35%) spitzoid lesions suspected for melanoma. H-RAS mutations were detected in 4 of 14 (29%) Spitz nevi, in 3 of 22 (14%) atypical Spitz nevi, in 1 of 15 (7%) spitzoid tumors suspected for melanoma, but in none of the spitzoid melanomas. These results strongly indicate that Spitz nevi and spitzoid melanomas are genetically unrelated entities. Furthermore, we can conclude that mutation analysis may be useful as an additional diagnostic tool to distinguish between benign and malignant spitzoid lesions.
"In the BRAF V600E mutation, a thymine at nucleotide 1799 on exon 15 is converted into adenine, causing glutamic acid to replace valine at residue 600. While BRAF V600E mutations have been described in congenital nevi , Spitz nevi , and blue nevi , they have been reported to occur with greatest frequency in acquired nevi (see Table 3) . BRAF mutations were first described in 81% (57 of 70) of acquired nevi studied by Pollock et al. in 2003 . "
[Show abstract][Hide abstract] ABSTRACT: Despite recent advances, the biology underlying nevogenesis remains unclear. Activating mutations in NRAS, HRAS, BRAF, and GNAQ have been identified in benign nevi. Their presence roughly correlates with congenital, Spitz, acquired, and blue nevi, respectively. These mutations are likely to play a critical role in driving nevogenesis. While each mutation is able to activate the MAP kinase pathway, they also interact with a host of different proteins in other pathways. The different melanocytic developmental pathways activated by each mutation cause the cells to migrate, proliferate, and differentiate to different extents within the skin. This causes each mutation to give rise to a characteristic growth pattern. The exact location and differentiation state of the cell of origin for benign moles remains to be discovered. Further research is necessary to fully understand nevus development given that most of the same developmental pathways are also present in melanoma.
Dermatology Research and Practice 04/2011; 2011(6):463184. DOI:10.1155/2011/463184
[Show abstract][Hide abstract] ABSTRACT: The rapid development of molecular biology in recent decades has dramatically changed the way we practice medicine. With the
help of an impressive arsenal of new technologies, including high-throughput sequencing and microarrays, we are now well-equipped
to probe into the molecular nature of diseases. Which set of genes are involved? What are the genetic and epigenetic alterations
associated with these genes? In this chapter, we will describe the basic concepts of molecular biology, including genes, types
of mutations, and gene expression.
[Show abstract][Hide abstract] ABSTRACT: At the end of the last decade, sporadic melanomas were still considered a genetic black box. Fortunately, in the last few years the box has been opened bringing to light melanoma-relevant oncogenes, aberrant signal transduction pathways, critical alterations in the melanoma cell cycle that go beyond p16INK4a, and melanoma- microenvironment interactions that are essential for tumor progression. This review will discuss some of the latest findings in melanoma research including the critical role of the MAPK pathway in the genesis of melanoma and senescence of nevi, the paradoxical tumor suppressor and oncogenic activities of the transcription factor MITF, and the unexpected oncogenic activities of the low molecular weight forms of cyclin E.
Frontiers in Bioscience 02/2006; 11(1):3003-13. DOI:10.2741/2028 · 3.52 Impact Factor
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