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000126891 1001_ $$0P:(DE-HGF)0$$aKoelsche, Christian$$b0$$eFirst author
000126891 245__ $$aMelanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles.
000126891 260__ $$aOxford$$bWiley-Blackwell$$c2015
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000126891 520__ $$aMelanotic tumors of the nervous system show overlapping histological characteristics but differ substantially in their biological behavior. In order to achieve a better delineation of such tumors, we performed an in-depth molecular characterization. Eighteen melanocytomas, 12 melanomas, and 14 melanotic and 14 conventional schwannomas (control group) were investigated for methylome patterns (450k array), gene mutations associated with melanotic tumors and copy number variants (CNVs). The methylome fingerprints assigned tumors to entity-specific groups. Methylation groups also showed a substantial overlap with histology-based diagnosis suggesting that they represent true biological entities. On the molecular level, melanotic schwannomas were characterized by a complex karyotype with recurrent monosomy of chromosome 22q and variable whole chromosomal gains and recurrent losses commonly involving chromosomes 1, 17p and 21. Melanocytomas carried GNAQ/11 mutations and presented with CNV involving chromosomes 3 and 6. Melanomas were frequently mutated in the TERT promoter, harbored additional oncogene mutations and showed recurrent chromosomal losses involving chromosomes 9, 10 and 6q, as well as gains of 22q. Together, melanotic nervous system tumors have several distinct mutational and chromosomal alterations and can reliably be distinguished by methylome profiling.
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000126891 7001_ $$0P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc$$aHovestadt, Volker$$b1$$udkfz
000126891 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b2$$udkfz
000126891 7001_ $$aCapper, David$$b3
000126891 7001_ $$0P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aSturm, Dominik$$b4$$udkfz
000126891 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b5$$udkfz
000126891 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b6$$udkfz
000126891 7001_ $$0P:(DE-HGF)0$$aAdeberg, Sebastian$$b7
000126891 7001_ $$aBöhmer, Katja$$b8
000126891 7001_ $$0P:(DE-He78)7df128638dc74f9d44caebe21ee14a9a$$aHagenlocher, Christian$$b9$$udkfz
000126891 7001_ $$aMechtersheimer, Gunhild$$b10
000126891 7001_ $$aKohlhof, Patricia$$b11
000126891 7001_ $$aMühleisen, Helmut$$b12
000126891 7001_ $$aBeschorner, Rudi$$b13
000126891 7001_ $$aHartmann, Christian$$b14
000126891 7001_ $$aBraczynski, Anne Kristin$$b15
000126891 7001_ $$aMittelbronn, Michel$$b16
000126891 7001_ $$aBuslei, Rolf$$b17
000126891 7001_ $$aBecker, Albert$$b18
000126891 7001_ $$aGrote, Alexander$$b19
000126891 7001_ $$aUrbach, Horst$$b20
000126891 7001_ $$aStaszewski, Ori$$b21
000126891 7001_ $$aPrinz, Marco$$b22
000126891 7001_ $$aHewer, Ekkehard$$b23
000126891 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b24$$udkfz
000126891 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b25$$udkfz
000126891 7001_ $$0P:(DE-HGF)0$$aReuss, David E$$b26
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