title: Primary melanocytic tumors of the central nervous system: a review with focus on molecular aspects.
abstract: Primary melanocytic tumors of the central nervous system (CNS) represent a spectrum of rare tumors. They can be benign or malignant and occur in adults as well as in children, the latter often in the context of neurocutaneous melanosis. Until recently, the genetic alterations in these tumors were largely unknown. This is in contrast with cutaneous and uveal melanomas, which are known to harbor distinct oncogenic mutations that can be used as targets for treatment with small-molecule inhibitors in the advanced setting. Recently, novel insights in the molecular alterations underlying primary melanocytic tumors of the CNS were obtained, including different oncogenic mutations in tumors in adult patients (especially GNAQ, GNA11) vs. children (especially NRAS). In this review, the focus is on molecular characteristics of primary melanocytic tumors of the CNS. We summarize what is known about their genetic alterations and discuss implications for pathogenesis and differential diagnosis with other pigmented tumors in or around the CNS. Finally, new therapeutic options with targeted therapy are discussed.
authors.affiliation: Department of Pathology, Canisius Wilhelmina Hospital, P.O. Box 9015, 6500 GS, Nijmegen.
authors.forename: Heidi V N
authors.initials: HV
authors.lastname: Küsters-Vandevelde
authors.forename: Benno
authors.initials: B
authors.lastname: Küsters
authors.forename: Adriana C H
authors.initials: AC
authors.lastname: van Engen-van Grunsven
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.forename: Willeke A M
authors.initials: WA
authors.lastname: Blokx
mesh_terms: D000818:Animals; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D015398:Signal Transduction
chemical_list: C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D008565:Membrane Proteins; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: GNA11; GNAQ; NRAS; brain; central nervous system; leptomeningeal melanocytic neoplasms; melanocytoma; melanoma; melanotic schwannoma; metastasis; molecular; mosaic RASopathy; neurocutaneous melanosis