Genetic alterations in melanocytic tumors.
In the last decade, significant progress has been made in our understanding of the genetic alterations in melanocytic tumors. The most exciting finding is the discovery of oncogenic BRAF mutations in both malignant melanoma and melanocytic nevi. This finding indicates that activation of the mitogen-activated protein kinase pathway may be a critical initiating step of melanocytic neoplasia, and that the fundamental difference between melanoma and nevi may lie in the inhibitory machinery for this oncogenic signaling. In addition, different genetic alterations identified in melanomas at different sites and with different levels of sun exposure have been shown, indicating that there are several distinct genetic pathways in the development of melanoma. Different patterns of genetic alterations have also been identified among different kinds of melanocytic nevi. While acquired nevi and small congenital nevi show a high frequency of BRAF mutations regardless of their anatomic localization, the mutations were rare in medium-sized congenital nevi and giant congenital nevi. Spitz nevi show no BRAF mutations, while a subset of cases show HRAS mutations, often associated with a copy number increase of chromosome 11p. The clear differences in genetic aberration patterns have significant clinical implications in the diagnosis and treatment of melanocytic tumors.
Takata
Minoru
M
Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. mtakata@hsp.md.shinshu-u.ac.jp
Saida
Toshiaki
T
D000818:Animals; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D019942:Genes, p16; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008545:Melanoma / Q000235:genetics*; D008546:Melanoma, Experimental / Q000235:genetics; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics; D009154:Mutation; D009508:Nevus, Pigmented / Q000235:genetics*; D009857:Oncogenes; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics
C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D025803:Tumor Suppressor Protein p14ARF; D019869:Phosphatidylinositol 3-Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)