gms | German Medical Science

Joint-Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN) and the Scandinavian Neuropathological Society (SNS)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

22.09.-24.09.2016, Hamburg

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Combined alterations in MAPK pathway genes, CDKN2A/B and ATRX characterize anaplastic pilocytic astrocytoma

Meeting Abstract

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  • presenting/speaker Annekathrin Kratz - University Hospital Heidelberg, Heidelberg, Germany, Department of Neuropathology, Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany
  • Felix Sahm - University Hospital Heidelberg, Heidelberg, Germany, Department of Neuropathology, Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany
  • Daniel Schrimpf - University Hospital Heidelberg, Heidelberg, Germany, Department of Neuropathology, Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany
  • David T. Jones - German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Division of Pediatric Neurooncology, Heidelberg, Germany
  • David Reuss - University Hospital Heidelberg, Heidelberg, Germany, Department of Neuropathology, Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany
  • Christian Koelsche - University Hospital Heidelberg, Heidelberg, Germany, Department of Neuropathology, Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany
  • Kristin Huang - University Hospital Heidelberg, Heidelberg, Germany, Department of Neuropathology, Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany
  • Annika K. Wefers - University Hospital Heidelberg, Heidelberg, Germany, Department of Neuropathology, Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany
  • Volker Hovestadt - German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Division of Molecular Genetics, Heidelberg, Germany
  • Dorothee Gramatzki - University Hospital and University of Zurich, Department of Neurology, Zurich, Switzerland; German Glioma Network, Bonn, Bochum, Dresden, Duesseldorf, Freiburg, Hamburg, Heidelberg, Munich, Tuebingen, Frankfurt, Germany
  • Joerg Felsberg - German Glioma Network, Bonn, Bochum, Dresden, Duesseldorf, Freiburg, Hamburg, Heidelberg, Munich, Tuebingen, Frankfurt, Germany; University of Duesseldorf, Institute for Neuropathology, Duesseldorf, Germany
  • Arend Koch - Charité Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany
  • Ulrich-W. Thomale - Charité Universitätsmedizin Berlin, Clinic for Pediatric Neurosurgery, Berlin, Germany
  • Guido Reifenberger - German Glioma Network, Bonn, Bochum, Dresden, Duesseldorf, Freiburg, Hamburg, Heidelberg, Munich, Tuebingen, Frankfurt, Germany; University of Duesseldorf, Institute for Neuropathology, Duesseldorf, Germany
  • Albert Becker - University of Bonn, Department of Neuropathology, Bonn, Germany
  • Volkmar Hans - University of Essen, Institute for Neuropathology, Essen, Germany
  • Marco Prinz - University of Freiburg, Institute for Neuropathology, Freiburg, Germany
  • Ori Staszewski - University of Freiburg, Institute for Neuropathology, Freiburg, Germany
  • Till Acker - University of Giessen, Institute of Neuropathology, Giessen, Germany
  • Hildegard Dohmen-Scheufler - University of Giessen, Institute of Neuropathology, Giessen, Germany
  • Christian Hartmann - Hannover Medical School, Department of Neuropathology, Hannover, Germany
  • Wolf Mueller - Leipzig University, Department of Neuropathology, Leipzig, Germany
  • Muin S. A. Tuffaha - Carl-Thiem-Klinikum Cottbus, Institute of Pathology, Cottbus, Germany
  • Werner Paulus - University of Muenster, Institute for Neuropathology, Muenster, Germany
  • Katharina Heß - University of Muenster, Institute for Neuropathology, Muenster, Germany
  • Benjamin Brokinkel - University of Muenster, Institute for Neuropathology, Muenster, Germany
  • Jens Schittenhelm - University of Tuebingen, Institute for Pathology and Neuropathology, Tuebingen, Germany
  • Camelia-Maria Monoranu - University of Wuerzburg, Comprehensive Cancer Center Mainfranken, Institute of Pathology, Department of Neuropathology, Wuerzburg, Germany
  • Almuth Friederike Kessler - University Hospital of Wuerzburg, Department of Neurosurgery, Wuerzburg, Germany
  • Almuth Friederike Kessler - Friedrich-Alexander University of Erlangen-Nuernberg (FAU), Institute for Neuropathology, Erlangen-Nuernberg, Germany
  • Mario Loehr - University Hospital of Wuerzburg, Department of Neurosurgery, Wuerzburg, Germany
  • Rolf Buslei - Friedrich-Alexander University of Erlangen-Nuernberg (FAU), Institute for Neuropathology, Erlangen-Nuernberg, Germany
  • Martina Deckert - University Hospital of Cologne, Department of Neuropathology, Cologne, Germany
  • Christian Mawrin - University of Magdeburg, Institute for Neuropathology, Magdeburg, Germany
  • Patricia Kohlhof - Katharinenhospital Stuttgart, Institute for Pathology, Stuttgart, Germany
  • Ekkehard Hewer - University of Bern, Institute of Pathology, Bern, Switzerland
  • Adriana Olar - The University of Texas MD Anderson Cancer Center, Dept. of Hematopathology, Molecular Diagnostic Laboratory, Houston, United States
  • Fausto Rodriguez - Johns Hopkins School of Medicine, Division of Neuropathology, Baltimore, United States
  • Caterina Giannini - Mayo Clinic, Minnesota, United States
  • Amulya A. NageswaraRao - Mayo Clinic, Minnesota, United States
  • Michael Weller - University Hospital and University of Zurich, Department of Neurology, Zurich, Switzerland; German Glioma Network, Bonn, Bochum, Dresden, Duesseldorf, Freiburg, Hamburg, Heidelberg, Munich, Tuebingen, Frankfurt, Germany
  • Ute Pohl - Queen’s Hospital, Department of Cellular Pathology, Romford, United Kingdom
  • Sebastian Brandner - UCL Institute of Neurology, Division of Neuropathology, London, United Kingdom
  • Stefan M. Pfister - German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Division of Pediatric Neurooncology, Heidelberg, Germany; University Hospital Heidelberg, Department of Pediatric Oncology and Hematology, Heidelberg, Germany
  • Andreas von Deimling - University Hospital Heidelberg, Heidelberg, Germany, Department of Neuropathology, Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany; German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
  • David Capper - University Hospital Heidelberg, Heidelberg, Germany, Department of Neuropathology, Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany; German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. Scandinavian Neuropathological Society. Joint-Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN) and the Scandinavian Neuropathological Society (SNS). Hamburg, 22.-24.09.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. Doc16dgnnP45

doi: 10.3205/16dgnn46, urn:nbn:de:0183-16dgnn463

Veröffentlicht: 14. September 2016

© 2016 Kratz et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Introduction: Tumors with histological features of pilocytic astrocytoma but with increased mitotic activity and additional high grade features (i.e. microvascular proliferation, necrosis) have been designated anaplastic pilocytic astrocytomas (APA). Patients with such tumors are thought to have an unfavorable clinical outcome.

Objectives: The status of APA as a separate entity has not yet been established and molecular features have only partially been elucidated. Therefore, the aim of this study was to systematically characterize APA molecularly.

Patients & Methods: We analyzed a large retrospective series of 98 cases with histological features of APA by genome wide DNA methylation profiling, copy number analysis, targeted sequencing and, in a subset, panel sequencing.

Results: Unsupervised hierarchical clustering analysis of 450k methylation data together with over 250 reference cases of 14 established glioma classes (glioblastoma, astrocytoma, oligodendroglioma, pleomorphic xanthoastrocytoma, pilocytic astrocytoma, ganglioglioma, dysembryoplastic neuroepithelial tumor and diffuse leptomeningeal glioneuronal tumor) allowed the identification of two distinct methylation clusters comprising 74 APAs. Most of the remaining cases clustered into other tumor classes. The median age of the APA cases was 42 years with only 5/67 (7%) cases occurring in pediatric patients. 53/66 (80%) caseswere located in the posterior fossa. The most frequent molecular alterations were deletions of CDKN2A/B (59/66, 89%) followed by alterations of the MAPK pathway (19/27, 70%, mostly NF1 mutations and BRAF fusions) and loss of ATRX (32/55, 45%). Outcome analysis confirmed an aggressive clinicalcourse with 13/20 (56%) patients deceased (median survival 13.4 months).

Conclusion: In summary, APA is characterized by increased patient age, predominant cerebellar location, frequent MAPK pathway alterations, CDKN2A/B deletion, ATRX loss and unfavorable prognosis.