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Comprehensive profiling of genetic alterations beyond\n                    <jats:italic>NF1<\/jats:italic>\n                    inactivation and epigenetic classification of these tumors remain limited. Through next-generation sequencing, copy number analysis, and DNA methylation profiling of gliomas from 47 NF1 patients, we identified 2 molecular subgroups of NF1-associated gliomas. The first harbored biallelic\n                    <jats:italic>NF1<\/jats:italic>\n                    inactivation only, occurred primarily during childhood, followed a more indolent clinical course, and had a unique epigenetic signature for which we propose the terminology \u201cpilocytic astrocytoma, arising in the setting of NF1\u201d. The second subgroup harbored additional oncogenic alterations including\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    homozygous deletion and\n                    <jats:italic>ATRX<\/jats:italic>\n                    mutation, occurred primarily during adulthood, followed a more aggressive clinical course, and was epigenetically diverse, with most tumors aligning with either high-grade astrocytoma with piloid features or various subclasses of IDH-wildtype glioblastoma. Several patients were treated with small molecule MEK inhibitors that resulted in stable disease or tumor regression when used as a single agent, but only in the context of those tumors with\n                    <jats:italic>NF1<\/jats:italic>\n                    inactivation lacking additional oncogenic alterations. Together, these findings highlight recurrently altered pathways in NF1-associated gliomas and help inform targeted therapeutic strategies for this patient population.\n                  <\/jats:p>","DOI":"10.1007\/s00401-022-02478-5","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T17:02:33Z","timestamp":1660064553000},"page":"747-765","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Multiplatform molecular analyses refine classification of gliomas arising in patients with neurofibromatosis type 1"],"prefix":"10.1007","volume":"144","author":[{"given":"Calixto-Hope G.","family":"Lucas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily 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