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61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

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Genetic risk profiles identify different molecular etiologies for glioma

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  • Matthias Simon - Neurochirurgische Klinik, Universitätskliniken Bonn, Deutschland
  • Fay J. Hosking - Institute of Cancer Research, Sutton, United Kingdom
  • Yannick Marie - Université Pierre et Marie Curie, Paris, France
  • Konstantin Gousias - Neurochirurgische Klinik, Universitätskliniken Bonn, Deutschland
  • Blandine Boisselier - Université Pierre et Marie Curie, Paris, France
  • Catherine Carpentier - Université Pierre et Marie Curie, Paris, France
  • Johannes Schramm - Neurochirurgische Klinik, Universitätskliniken Bonn, Deutschland
  • Karima Mokhtari - Université Pierre et Marie Curie, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Neuropathologie R Escourolle, Paris, France
  • Khe Hoang-Xuan - Université Pierre et Marie Curie, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France
  • Ahmed Idbaih - Université Pierre et Marie Curie, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France
  • Jean-Yves Delattre - Université Pierre et Marie Curie, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France
  • Mark Lathrop - Fondation Jean-Dausset-CEPH et Centre National de Génotypage du CEA, Evry Cedex, France
  • Lindsay B. Robertson - Institute of Cancer Research, Sutton, United Kingdom
  • Richard S. Houlston - Institute of Cancer Research, Sutton, United Kingdom
  • Marc Sanson - Université Pierre et Marie Curie, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, Paris, France

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocV1548

doi: 10.3205/10dgnc025, urn:nbn:de:0183-10dgnc0259

Published: September 16, 2010

© 2010 Simon 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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Objective: Genome-wide association studies have recently identified single nucleotide polymorphisms in five loci at 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756, CDKN2A/CDKN2B), 20q13.33 (rs6010620, RTEL1) and 11q23.3 (rs498872, PHLDB1) to be associated with glioma risk. Since gliomas are heterogeneous in histology, molecular alterations and clinical behavior we have investigated these polymorphisms for potential correlations with tumor histology and patient survival.

Methods: We studied the relationship between SNPs and glioma subtype in two large patient cohorts from France and Germany, totaling 1,577 patients. Also studied was the relationship between SNP-genotype and overall survival.

Results: In both cohorts the frequencies of rs2736100 and rs6010620 risk genotypes were highly correlated with high-grade disease (P<0.001) while rs4295627 and rs498872 risk genotypes were inversely related to tumor grade (P<0.001). These data show that genetic variation at these loci have sub-type specific effects on the risk of developing glioma. In contrast rs4977756 genotype was not correlated with tumor grade consistent with the causal variant having a generic influence on glioma development. None of the five SNPs were associated with prognosis, independent of tumor grade.

Conclusions: Our findings provide novel insight into etiological pathways in the different glioma subtypes.