{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:58:21Z","timestamp":1790834301689,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,4,2]],"date-time":"2017-04-02T00:00:00Z","timestamp":1491091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent <jats:italic>BRAF<\/jats:italic> V600E mutation and <jats:italic>CDKN2A\/B<\/jats:italic> deletion. We explored the association of copy\u2010number variants (CNVs) with <jats:italic>BRAF<\/jats:italic> mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A\u2010PXA), 23 <jats:italic>BRAF<\/jats:italic> V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous <jats:italic>CDKN2A\/B<\/jats:italic> deletion (n\u2009=\u200933, 87%), a higher proportion than previously detected by comparative genomic hybridization (50%\u201360%) (37). <jats:italic>CDKN2A\/B<\/jats:italic> deletion was present in similar proportion of PXA (83%), A\u2010PXA (93%), <jats:italic>BRAF<\/jats:italic> V600E (87%), and wild\u2010type (87%) tumors. Whole chromosome gains\/losses were frequent, including gains +7 (n\u2009=\u200915), +2 (n\u2009=\u200911), +5 (n\u2009=\u200910), +21 (n\u2009=\u200910), +20 (n\u2009=\u20099), +12 (n\u2009=\u20098), +15 (n\u2009=\u20098), and losses \u221222 (n\u2009=\u200911), \u221214 (n\u2009=\u20097), \u221213 (n\u2009=\u20095). Losses and copy\u2010neutral loss of heterozygosity were significantly more common in A\u2010PXA, involving chromosomes 22 (<jats:italic>P<\/jats:italic>\u2009=\u20090.009) and 14 (<jats:italic>P<\/jats:italic>\u2009=\u20090.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (<jats:italic>P<\/jats:italic>\u2009=\u20090.003), while other copy\u2010number changes, including <jats:italic>CDKN2A\/B<\/jats:italic> deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A\u2010PXA with areas of distinct low\u2010 and high\u2010grade morphology (n\u2009=\u20092), matched primary\/tumor recurrence (n\u2009=\u20097), or both (n\u2009=\u20091). Copy\u2010number changes on recurrence\/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy\u2010number changes. Overall, we confirm <jats:italic>CDKN2A\/B<\/jats:italic> deletion as key a feature of PXA not associated with tumor grade or <jats:italic>BRAF<\/jats:italic> mutation, but central to the underlying genetics of PXA.<\/jats:p>","DOI":"10.1111\/bpa.12495","type":"journal-article","created":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T08:43:05Z","timestamp":1486629785000},"page":"172-182","source":"Crossref","is-referenced-by-count":75,"title":["Recurrent copy number alterations in low\u2010grade and anaplastic pleomorphic xanthoastrocytoma with and without <i>BRAF<\/i> V600E mutation"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8842-5975","authenticated-orcid":false,"given":"Rachael A.","family":"Vaubel","sequence":"first","affiliation":[{"name":"From the Departments of Anatomic Pathology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alissa 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MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amulya A.","family":"Nageswara Rao","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\u2010Oncology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lachance","sequence":"additional","affiliation":[{"name":"Neurology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Parney","sequence":"additional","affiliation":[{"name":"Neurologic Surgery, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Giannini","sequence":"additional","affiliation":[{"name":"From the Departments of Anatomic Pathology, Mayo Clinic, Rochester, 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