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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

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MAPK pathway activation by GNAQ and GNA11 mutations in melanocytic tumors of the central nervous system.

Meeting Abstract

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  • presenting/speaker Marco Gessi - University of Bonn Medical Center, Inst. of Neuropathology, Bonn, Germany
  • Jennifer Hammes - University of Bonn Medical Center, Inst. of Neuropathology, Bonn, Germany
  • Libero Lauriola - Catholic University, Dept. of Pathology, Rome, Italy
  • Evelyn Dörner - University of Bonn Medical Center, Inst. of Neuropathology, Bonn, Germany
  • Jutta Kirfel - University of Bonn Medical Center, Inst. of Pathology, Bonn, Germany
  • Glen Kristiansen - University of Bonn Medical Center, Inst. of Pathology, Bonn, Germany
  • Anja zur Muehlen - University of Bonn Medical Center, Inst. of Neuropathology, Bonn, Germany
  • Dorota Denkhaus - University of Bonn Medical Center, Inst. of Neuropathology, Bonn, Germany
  • Andreas Waha - University of Bonn Medical Center, Inst. of Neuropathology, Bonn, Germany
  • Torsten Pietsch - University of Bonn Medical Center, Inst. of Neuropathology, Bonn, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP3.24

doi: 10.3205/12dgnn068, urn:nbn:de:0183-12dgnn0682

Published: September 11, 2012

© 2012 Gessi et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Activation of the mitogen-activated protein kinase (MAPK) pathway, leading to over-expression of p-ERK is considered to be pivotal for melanocytes proliferation and considered an early event in melanoma development. In melanocytic tumor of the CNS, such event seems however not to depend on activating BRAF or N-RAS mutations, as observed in cutaneous melanocytic nevi as well as melanomas. The MAPK activation may, however, be dependent on alterations of other genes such as GNAQ, GNA11 and KIT, which have been found frequently mutated in uveal melanomas, the melanoma subtype which shows some histological and molecular similarities to melanocytic tumors of the CNS. In this study, we investigated the mutational status of GNAQ, GNA11, KIT, BRAF, N-RAS and H-RAS in a series of 21 melanocytic tumors of the CNS with a combined pyrosequencing-based, SSCP-based and High Melting Resolution Analysis (HRM)-based approach. The series included 7 melanocytomas, 10 melanocytomas of intermediate differentiation and 4 primary CNS melanomas. 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 detected in the HRM analysis. All identified mutations were mutually exclusive. In the SSCP analysis, no shifts corresponding to BRAFV600E mutations or suggesting mutations in exons 9, 11, 13, 17 of the KIT gene were observed. In conclusion, GNA11 mutations represent an alternative mechanism of MAPK pathway activation in melanocytic tumors of the CNS. Our data confirm also the presence of frequent activating mutations of GNAQ and the occurrence of sporadic N-RAS mutations in such tumors. On the other hand, mutations affecting BRAF and KIT, in contrast to cutaneous melanomas, are absent or very rare in primary melanocytic tumors of the CNS.