{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:41:27Z","timestamp":1791380487822,"version":"4.3.3"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70112956"],"award-info":[{"award-number":["70112956"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70110983"],"award-info":[{"award-number":["70110983"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Meningiomas are classified based on histological features, but genetic and epigenetic features are emerging as relevant biomarkers for outcome prediction and may supplement histomorphological evaluation. We investigated meningioma\u2010relevant mutations and their correlation with DNA methylation clusters and patient survival times. Formalin\u2010fixed and paraffin\u2010embedded samples of 126 meningioma patients (WHO grade I 52\/126; 41.3%; WHO grade II: 48\/126; 38.1%; WHO grade III: 26\/126; 20.6%) were investigated. We analyzed\n                    <jats:italic>NF2, TRAF7, KLF4, ARID, SMO, AKT,<\/jats:italic>\n                    <jats:italic>TERT<\/jats:italic>\n                    promotor,\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    , and\n                    <jats:italic>SUFU<\/jats:italic>\n                    mutations using panel sequencing and correlated them to DNA methylation classes (MC) determined using 850k EPIC arrays. The TRAKL mutation genotype was characterized by the presence of any of the following mutations:\n                    <jats:italic>TRAF7, AKT1<\/jats:italic>\n                    , and\n                    <jats:italic>KLF4<\/jats:italic>\n                    . Survival data including progression\u2010free survival (PFS) and overall survival (OS) was retrieved from chart review. Mutations were evident in 90\/126 (71.4%) specimens with mutations in\n                    <jats:italic>NF2<\/jats:italic>\n                    (39\/126; 31.0%),\n                    <jats:italic>TRAF7<\/jats:italic>\n                    (39\/126; 31.0%) and\n                    <jats:italic>KLF4<\/jats:italic>\n                    (25\/126; 19.8%) being the most frequent ones. Two or more mutations were observed in 35\/126 (27.8%) specimens. While\n                    <jats:italic>TRAKL<\/jats:italic>\n                    was predominantly found in benign MC, NF2 was associated with malign MC (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05).\n                    <jats:italic>TRAF7, KLF4<\/jats:italic>\n                    , and TRAKL mutation genotype were associated with improved PFS and OS (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05).\n                    <jats:italic>TERT<\/jats:italic>\n                    promotor methylation, intermediate, and malign MC were associated with impaired PFS and OS (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). Methylation cluster showed better prognostic discrimination for PFS and OS (c\u2010index 0.77\/0.75) than each of the individual mutations (c\u2010index 0.63\/0.68). In multivariate analysis correcting for age, gender, MC, and WHO grade, none of the individual mutations except TERT remained an independent significant prognostic factor for PFS. Molecular profiling including mutational analysis and DNA methylation classification may facilitate more precise prognostic assessment and identification of potential targets for personalized therapy in meningioma patients.\n                  <\/jats:p>","DOI":"10.1111\/bpa.12970","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T10:33:33Z","timestamp":1645785213000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Prognostic impact of genetic alterations and methylation classes in meningioma"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9379-6797","authenticated-orcid":false,"given":"Anna S.","family":"Berghoff","sequence":"first","affiliation":[{"name":"Division of Oncology Department of Medicine I Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hielscher","sequence":"additional","affiliation":[{"name":"Division of Biostatistics German Cancer Research Center (DKFZ  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerda","family":"Ricken","sequence":"additional","affiliation":[{"name":"Institute of Neurology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Furtner","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image\u2010guided Therapy Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Schrimpf","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Neuropathology German Cancer Consortium German Cancer Research Center  Heidelberg Germany"},{"name":"Department of Neuropathology Institute of Pathology University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Widhalm","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Rajky","sequence":"additional","affiliation":[{"name":"Division of Oncology Department of Medicine I Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Marosi","sequence":"additional","affiliation":[{"name":"Division of Oncology Department of Medicine I Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A.","family":"Hainfellner","sequence":"additional","affiliation":[{"name":"Institute of Neurology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"von Deimling","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Neuropathology German Cancer Consortium German Cancer Research Center  Heidelberg Germany"},{"name":"Department of Neuropathology Institute of Pathology University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Sahm","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Neuropathology German Cancer Consortium German Cancer Research Center  Heidelberg Germany"},{"name":"Department of Neuropathology Institute of Pathology University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3541-2315","authenticated-orcid":false,"given":"Matthias","family":"Preusser","sequence":"additional","affiliation":[{"name":"Division of Oncology Department of Medicine I Medical University of Vienna  Vienna 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