{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:00:04Z","timestamp":1790751604692,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012634","name":"Novocure","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012634","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tumor treating fields (TTFields) are a treatment for glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH wt) that improves survival, but no validated biomarkers exist to identify patients likely to benefit. This study aims to identify molecular biomarkers guiding clinical decisions on TTFields initiation. Eighty gliomas treated with surgery, radiochemotherapy, and TTFields were reassessed using DNA methylation profiling and TSO500 DNA\/RNA panel sequencing, identifying 64 highly characteristic GBM, IDH wt with comprehensive molecular data. Alterations present in \u22655 cases were analyzed for association with survival using Kaplan\u2013Meier and Cox models. Two TTFields\u2010na\u00efve GBM, IDH wt cohorts (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009175) served as controls. For 18 cases, post\u2010treatment tissue from a second surgery was profiled. Twenty\u2010four alterations occurred in \u22655 patients. Univariate analyses showed KPS and\n                    <jats:italic>MGMT<\/jats:italic>\n                    promoter methylation as protective, while\n                    <jats:italic>EGFR<\/jats:italic>\n                    amplification,\n                    <jats:italic>CDKN2A\/B<\/jats:italic>\n                    loss, and homozygous\n                    <jats:italic>PTEN<\/jats:italic>\n                    deletion were linked to worse survival with TTFields. Multivariate analysis confirmed KPS and MGMT as protective and homozygous\n                    <jats:italic>PTEN<\/jats:italic>\n                    deletion as a risk factor (median OS 368 vs. 603\u2009days; HR 3.86,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0049). In TTFields\u2010na\u00efve cohorts, homozygous\n                    <jats:italic>PTEN<\/jats:italic>\n                    deletion was not associated with outcome, and frequencies were comparable (controls 7%, TTFields 11%). Post\u2010TTFields GBM, IDH wt did not acquire hypermutation or other recurrent molecular alterations. Alongside the established factors\n                    <jats:italic>MGMT<\/jats:italic>\n                    and KPS,\n                    <jats:italic>PTEN<\/jats:italic>\n                    homozygous deletion was associated with worse survival in GBM, IDH wt patients treated with TTFields. Homozygous\n                    <jats:italic>PTEN<\/jats:italic>\n                    deletion may be associated with reduced benefit from TTFields and should be further investigated as a predictive biomarker for TTFields treatment.\n                  <\/jats:p>","DOI":"10.1111\/bpa.70143","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T01:56:21Z","timestamp":1789091781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>PTEN<\/i>\n                    homozygous deletion is a negative prognostic factor in tumor treating fields\u2010treated glioblastoma,\n                    <scp>IDH<\/scp>\n                    wildtype patients"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6906-4339","authenticated-orcid":false,"given":"Jakob","family":"N\u00fcckles","sequence":"first","affiliation":[{"name":"Department of Neuropathology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudius","family":"Jelgersma","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7625-6569","authenticated-orcid":false,"given":"Christin","family":"Siewert","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin  Berlin 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