title: GNA11 and N-RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central nervous system.
abstract: OBJECTIVE
  Primary melanocytic tumours are uncommon neoplasms of the central nervous system. Although similarities with uveal melanomas have been hypothesized, data on their molecular features are limited.
  
  
  METHODS
  In this study, we investigated the mutational status of BRAF(V600E) , KIT, GNAQ, GNA11, N-RAS and H-RAS in a series of 19 primary melanocytic tumours of the central nervous system (CNS).
  
  
  RESULTS
  We identified six cases harbouring mutations in the hotspot codon 209 of the GNAQ gene and two cases with mutations in the hotspot codon 209 of the GNA11 gene. Two mutations in codon 61 of N-RAS were also found. In the single strand conformation polymorphism (SSCP) analysis, no shifts corresponding to BRAF(V600E) mutations or suggesting activating mutations in the KIT gene were observed.
  
  
  CONCLUSIONS
  In primary melanocytic tumours of the CNS, GNA11 and N-RAS mutations represent a mechanism of MAPK pathway activation alternative to the common GNAQ mutations. On the other hand, BRAF(V600E) mutations and activating KIT mutations seem to be absent or very rare in these tumours.
authors: Inst. of Neuropathology, University of Bonn Medical Center, 53127 Bonn, Germany. mgessimd@yahoo.com
authors: M
authors: M
authors: Gessi
authors: J
authors: J
authors: Hammes
authors: L
authors: L
authors: Lauriola
authors: E
authors: E
authors: Dörner
authors: J
authors: J
authors: Kirfel
authors: G
authors: G
authors: Kristiansen
authors: A
authors: A
authors: zur Muehlen
authors: D
authors: D
authors: Denkhaus
authors: A
authors: A
authors: Waha
authors: T
authors: T
authors: Pietsch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016543:Central Nervous System Neoplasms / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000235:genetics* / Q000502:physiology*; D008297:Male; D008544:Melanocytes / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D043802:GTP-Binding Protein alpha Subunits, Gq-G11