{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:53:02Z","timestamp":1772160782360,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Mutations activating the hedgehog (Hh) signalling pathway have been described in anterior skull base meningiomas, raising hope for the use of targeted therapies. However, identification of Hh\u2010activated tumours is hampered by the lack of a reliable immunohistochemical marker. We report the evaluation of GAB1, an immunohistochemical marker used to detect Hh pathway activation in medulloblastoma, as a potential marker of Hh\u2010activated meningiomas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      GAB1\u00a0staining was compared to\n                      <jats:italic>SMO<\/jats:italic>\n                      mutation detection with Sanger and NGS techniques as well as Hh pathway activation study through mRNA expression level analyses in a discovery set of 110 anterior skull base meningiomas and in a prospective validation set of 21\u00a0meningiomas.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Using an expression score ranging from 0 to 400, we show that a cut\u2010off score of 250\u00a0lead to excellent detection of Hh pathway mutations (sensitivity 100%, specificity 86%). The prospective validation set confirmed the excellent negative predictive value of GAB1 to exclude Hh\u2010independent meningiomas. We describe a large series of 32\n                      <jats:italic>SMO<\/jats:italic>\n                      \u2010mutant meningiomas and define multiple ways of Hh activation, either through somatic mutations or associated with mutually co\u2010exclusive sonic hedgehog (SHH) or Indian hedgehog (IHH) overexpression independent of the mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The assessment of GAB1 expression by an immunohistochemical score is a fast and cost\u2010efficient tool to screen anterior skull base meningiomas for activation of the Hh pathway. It could facilitate the identification of selected cases amenable to sequencing for Hh pathway genes as predictive markers for targeted therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12740","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T04:40:32Z","timestamp":1622436032000},"page":"748-755","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["GAB1 overexpression identifies hedgehog\u2010activated anterior skull base meningiomas"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2572-8594","authenticated-orcid":false,"given":"Julien","family":"Boetto","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Gui de Chauliac Hospital Montpellier University Hospital Center  Montpellier France"},{"name":"ICM INSERM U1127 CNRS UMR 7225 Paris Brain Institute  Paris 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06  Paris France"},{"name":"Department of Neuropathology AP\u2010HP H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline","family":"Marijon","sequence":"additional","affiliation":[{"name":"ICM INSERM U1127 CNRS UMR 7225 Paris Brain Institute  Paris France"},{"name":"Department of Neurosurgery AP\u2010HP H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Kalamarides","sequence":"additional","affiliation":[{"name":"ICM INSERM U1127 CNRS UMR 7225 Paris Brain Institute  Paris France"},{"name":"Department of Neurosurgery AP\u2010HP H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"},{"name":"Sorbonne Universit\u00e9 UPMC Univ Paris 06  Paris 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