Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles

Christian Koelsche, Volker Hovestadt, David T.W. Jones, David Capper, Dominik Sturm, Felix Sahm, Daniel Schrimpf, Sebastian Adeberg, Katja Böhmer, Christian Hagenlocher, Gunhild Mechtersheimer, Patricia Kohlhof, Helmut Mühleisen, Rudi Beschorner, Christian Hartmann, Anne Kristin Braczynski, Michel Mittelbronn, Rolf Buslei, Albert Becker, Alexander GroteHorst Urbach, Ori Staszewski, Marco Prinz, Ekkehard Hewer, Stefan M. Pfister, Andreas Von Deimling, David E. Reuss*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

58 Citations (Scopus)


Melanotic 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.

Original languageEnglish
Pages (from-to)202-208
Number of pages7
JournalBrain Pathology
Issue number2
Publication statusPublished - 1 Mar 2015
Externally publishedYes


  • 450k
  • GNA11
  • GNAQ
  • TERT promoter
  • copy number variants
  • melanocytoma
  • melanoma
  • melanotic schwannoma


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