Citations 2
Intracranial mesenchymal tumor, FET::CREB fusion-positive: An integrative analysis of 81 cases
Rajan, Sharika, Chung, Hye‐Jung, Wu, Zhichao , Dazelle, Karen , Abdullaev, Zied , Tyagi, Manoj, Ferrone, Christina K. , Raffeld, Mark , Lee, Ina, Chen, Jie , Cathcart, Sahara , Giannini, C., Nguyen, Aivi, Gökden, Murat , Perry, A., Fernandes, Igor Lima , Putnam, Angelica R. , Kurek, Kyle C., Green, Richard M, Lucas, Calixto-Hope, González-Gómez, Ignacio, Lopez, G., Ra, Prayson, Yeaney, Gabrielle , Dermawan, Josephine Kam Tai, Chkheidze, Rati , Appin, Christina , Uhlmann, Erik J. , Taliansky, A , Blessing, Melissa M. , Mohila, Carrie, Deisch, Jeremy , Andreiuolo, Felipe, Crawford, John R, Stemmer‐Rachamimov, Anat , Lakis, Nelli S., Re, Schmidt, Chacko, Geeta, Newbury, Robert, Neill, Stewart G. , Morales, Bryan , Fecher, Roger , Sloan, Emily A. , Solomon, David A, Nasrallah, MacLean, Quezado, Martha, Aldape, Kenneth, Solomon, David A. , Chen, Jie , Giannini, Caterina , Perry, Arie , Chkheidze, Rati , Deisch, Jeremy , Solomon, David A , Aldape, Kenneth , Jones, Karra A , López, Giselle Y. , Wu, Zhichao, Singh, Omkar, Gagan, Jeffrey , Nguyen, Aivi, Perry, Arie , Green, Richard M., Eberhart, Charles G. , Lucas, Calixto-Hope C. , Jones, Karra A. , Mohila, Carrie , Cotter, Jennifer A. , Andreiuolo, Felipe , Crawford, John R, Mount, Christopher , Lakis, Nelli S., Schmidt, Robert, Chacko, Geeta , Nasrallah, MacLean P. , Quezado, Martha , Fonseca, Adriana
Neuro-Oncology | January 17, 2026 | Volume: 28 | Issue: 4 | Pages: 939-951
Abstract Background Intracranial mesenchymal tumors, FET::CREB fusion-positive (ICMT), show fusions involving FET RNA-binding protein family genes (EWSR1 or FUS) and CREB family of transcription factors (ATF1, CREB1, or CREM). The methylation signature(s), gene expression characteristics, and clinical behavior of this important tumor type require further characterization. Methods We study the methylation profiles of 81 ICMT cases (61 newly profiled cases and 20 cases from publicly available sources). Clinicopathologic and genomic data were recorded for each case when available. Results ICMT showed a relatively distinct methylation signature compared to related tumors. Among the 65 cases where fusion types were documented, the identified fusions included EWSR1::ATF1 (25 cases), EWSR1::CREB1 (12 cases), EWSR1::CREM (21 cases), FUS::CREM (3 cases), and SMARCA2::CREM (4 cases). We confirmed the prior description of 2 distinct subgroups of ICMT (subclasses A and B). The majority of the cases belonged to subclass A (n = 69; 85%), which showed a higher median age compared to subclass B patients (26 years vs. 15 years). Subclass B cases (n = 12; 15%) showed shorter progression-free survival (P < 0.01). Gene expression analysis of ICMT showed key overexpressed markers in ICMT, with significant CREM overexpression regardless of fusion type, when compared to either meningioma alone or a larger group of CNS tumors. Conclusions This work provides further characterization of ICMT as an important CNS mesenchymal neoplasm that is prone to tumor recurrence, showing 2 prognostically relevant methylation subclasses and warranting diagnostic distinction from other epigenetically and histologically related tumors. ICMTs show substantial overexpression of the CREM gene, independent of fusion type.
Molecular, histologic, and clinical characterization of methylation class pleomorphic xanthoastrocytoma: An analysis of 469 tumors
Dampier, Christopher H. , Shah, Niharika, Neto, Osório Lopes Abath , Abdullaev, Zied , Alexandrescu, Sanda , Armstrong, Terri, Baker, Tiffany , Cathcart, Sahara , Chung, Hye‐Jung, Cimino, Patrick J. , Conway, Kyle , Dazelle, Karen , Etminam, Nima, Fernandes, Igor, Ferrone, Christina K. , Gilani, Ahmed , Gilbert, Mark, Gregory, Jason V. , Lee, Han Sung, Lopes, Maria Beatriz, Neill, Stewart G. , Ozer, Byram H. , Paulus, Werner, Penas‐Prado, Marta, Prinz, Marco , Pytel, Peter , Quezado, Martha , Raffeld, Mark , Rajan, Sharika, Reifenberger, Guido, Robinson, Lorraina , Schittenhelm, Jens , Thomas-Ogunniyi, Jaiyeola , Toland, Angus , Turakulov, Rust , Aldape, Kenneth , Cimino, Patrick J , Mao, Qinwen , Prinz, Marco , Ratliff, Miriam , Robinson, Lorraina , Schittenhelm, Jens , Thomas, Christian , Vaubel, Rachael A , Wu, Jing , Giannini, Caterina , Brandner, Sebastian , von Deimling, Andreas , Aldape, Kenneth , Dampier, Christopher H , Galbraith, Kristyn , Ebrahimi, Azadeh , Andreiuolo, Felipe , Cotter, Jennifer A. , Costa, Felipe D’Almeida , Ferman, Sima , Fernandes, Igor, Gregory, Jason, Ketchum, Courtney , Lee, Ina , Lopes, M. Beatriz S. , Mao, Qinwen , Marshall, Michael S. , McCord, Matthew , Nirschl, Jeffrey , Peñas-Prado, Marta , Schrimpf, Daniel , Singh, Omkar , Thomas, Christian , Thomas, Diana , Vaubel, Rachael A. , Wadhwani, Nitin R. , Giannini, Caterina , Snuderl, Matija , Deimling, Andreas von
Neuro-Oncology Advances | July 21, 2025 | Volume: 7 | Issue: 1 | Pages: No page available
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-grade histologic features can help predict their clinical behavior. The use of an epigenetic classification of PXA reveals that this group of tumors is more common than previously appreciated and warrants in-depth study to identify efficacious therapeutic options.