Molecular, histologic, and clinical characterization of methylation class pleomorphic xanthoastrocytoma: An analysis of 469 tumors

作者：Christopher H. Dampier, Niharika Shah, Kristyn Galbraith, Azadeh Ebrahimi, Osório Lopes Abath Neto, Zied Abdullaev, Sanda Alexandrescu, Felipe Andreiuolo, Terri Armstrong, Tiffany Baker, Sahara Cathcart, Hye‐Jung Chung, Patrick J. Cimino, Kyle Conway, Jennifer Cotter, Felipe D’Almeida Costa, Karen Dazelle, Nima Etminam, Sima Ferman, Igor Fernandes, Christina K. Ferrone, Ahmed Gilani, Mark Gilbert, Jason V. Gregory, Courtney Ketchum, Han Sung Lee, Ina Lee, Maria Beatriz Lopes, Qinwen Mao, Michael S. Marshall, Matthew McCord, Stewart G. Neill, Jeffrey Nirschl, Byram H. Ozer, Werner Paulus, Marta Penas‐Prado, Marco Prinz, Peter Pytel, Martha Quezado, Mark Raffeld, Sharika Rajan, Miriam Ratliff, Guido Reifenberger, Lorraina Robinson, Jens Schittenhelm, Daniel Schrimpf, Omkar Singh, Christian Thomas, Diana Thomas, Jaiyeola Thomas-Ogunniyi, Angus Toland, Rust Turakulov, Rachael A. Vaubel, Nitin R. Wadhwani, Jing Wu, Caterina Giannini, Matija Snuderl, Sebastian Brandner, Andreas von Deimling, Kenneth Aldape · 发表于：Neuro-Oncology Advances · 年份：2025 · DOI：10.1093/noajnl/vdaf089 · 被引用次数：5 · 研究领域：Glioma Diagnosis and Treatment、Cancer, Hypoxia, and Metabolism、Ubiquitin and proteasome pathways

Abstract Background Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM). Methods To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.85) was interrogated. Results Patient median age was 23 years (range 1-73 years) with a female predominance (259 female/199 male). CDKN2A/B homozygous deletion was observed in 406 of 469 (87%) samples. In samples tested for BRAF p.V600E mutations (n = 279), 240 (86%) harbored the mutation. A chr7+/chr10− pattern was observed in 103 of 469 (22%) samples. Among samples tested for TERT promoter mutations (n = 143), 32 (22%) harbored the mutation. Progression-free and overall survival of patients with mcPXA were comparable to patients with methylation class IDH-mutant astrocytoma, low grade, but a GBM-like subset (ie, cases with a pre-methylation working diagnosis of GBM) showed shorter survival. Histologic features of high grade, including palisading necrosis and microvascular proliferation, were prognostic in mcPXA. Compared to patients with BRAF p.V600E-altered GBM, patients with mcPXA were younger and had a lower frequency of TERT promoter mutations. Conclusion Tumors in mcPXA share molecular characteristics with histologically defined PXA, and high-...