Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations

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Details zur Publikation

Autorinnen und Autoren: Reinhardt A, Stichel D, Schrimpf D, Sahm F, Korshunov A, Reuss DE, Koelsche C, Huang K, Wefers AK, Hovestadt V, Sill M, Gramatzki D, Felsberg J, Reifenberger G, Koch A, Thomale UW, Becker A, Hans VH, Prinz M, Staszewski O, Acker T, Dohmen H, Hartmann C, Mueller W, Tuffaha MSA, Paulus W, Hess K, Brokinkel B, Schittenhelm J, Monoranu CM, Kessler AF, Loehr M, Buslei R, Deckert M, Mawrin C, Kohlhof P, Hewer E, Olar A, Rodriguez FJ, Giannini C, Nageswararao AA, Tabori U, Nunes NM, Weller M, Pohl U, Jaunmuktane Z, Brandner S, Unterberg A, Haenggi D, Platten M, Pfister SM, Wick W, Herold-Mende C, Jones DTW, Von Deimling A, Capper D
Zeitschrift: Acta Neuropathologica
Jahr der Veröffentlichung: 2018
Band: 136
Heftnummer: 2
Seitenbereich: 273-291
ISSN: 0001-6322


Abstract

Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas. T-distributed stochastic neighbor-embedding (t-SNE) and hierarchical clustering analysis of these 102 cases against 158 reference cases from 12 glioma reference classes revealed that a subset of 83 of these tumors share a common DNA methylation profile that is distinct from the reference classes. These 83 tumors were thus denominated DNA methylation class anaplastic astrocytoma with piloid features (MC AAP). The 19 remaining tumors were distributed amongst the reference classes, with additional testing confirming the molecular diagnosis in most cases. Median age of patients with MC AAP was 41.5 years. The most frequent localization was the posterior fossa (74%). Deletions of CDKN2A/B (66/83, 80%), MAPK pathway gene alterations (49/65, 75%, most frequently affecting NF1, followed by BRAF and FGFR1) and mutations of ATRX or loss of ATRX expression (33/74, 45%) were the most common molecular alterations. All tumors were IDH1/2 wildtype. The MGMT promoter was methylated in 38/83 tumors (45%). Outcome analysis confirmed an unfavorable clinical course in comparison to PA, but better than IDH wildtype glioblastoma. In conclusion, we show that a subset of histologically defined anaplastic pilocytic astrocytomas forms a separate DNA methylation cluster, harbors recurrent alterations in MAPK pathway genes in combination with alterations of CDKN2A/B and ATRX, affects patients who are on average older than those diagnosed with PA and has an intermediate clinical outcome.


Zusätzliche Organisationseinheit(en)
Neuropathologisches Institut


Einrichtungen weiterer Autorinnen und Autoren

Albert-Ludwigs-Universität Freiburg
Carl-Thiem-Klinikum
Charité - Universitätsmedizin Berlin
Deutsches Krebsforschungszentrum (DKFZ)
Eberhard Karls Universität Tübingen
Heinrich-Heine-Universität Düsseldorf
Johns Hopkins University
Julius-Maximilians-Universität Würzburg
Justus-Liebig-Universität Gießen
Katharinenhospital Stuttgart
King's College Hospital (KCH)
Mayo Clinic
Medical University of South Carolina (MUSC)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Otto-von-Guericke-Universität Magdeburg
Queen's Hospital
Rheinische Friedrich-Wilhelms-Universität Bonn
Ruprecht-Karls-Universität Heidelberg
Sozialstiftung Bamberg
Universität Bern
Universität Duisburg-Essen (UDE)
Universität Leipzig
Universitätsklinikum Heidelberg
Universitätsklinikum Köln
Universitätsklinikum Mannheim
Universitätsklinikum Münster
Universitätsklinikum Würzburg
Universitätsspital Zürich (USZ)
University of Toronto


Zitierweisen

APA:
Reinhardt, A., Stichel, D., Schrimpf, D., Sahm, F., Korshunov, A., Reuss, D.E.,... Capper, D. (2018). Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations. Acta Neuropathologica, 136(2), 273-291. https://dx.doi.org/10.1007/s00401-018-1837-8

MLA:
Reinhardt, Annekathrin, et al. "Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations." Acta Neuropathologica 136.2 (2018): 273-291.

BibTeX: 

Zuletzt aktualisiert 2019-20-03 um 16:08