Zurück zur Übersicht
| Acta neuropathologica. 2021 Aug 21. doi: 10.1007/s00401-021-02354-8. pii: 10.1007/s00401-021-02354-8 |
| PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum. |
| Alhalabi KT1, Stichel D2, Sievers P3, Peterziel H4, Sommerkamp AC5, Sturm D6, Wittmann A7, Sill M8, Jäger N9, Beck P10, Pajtler KW11, Snuderl M12, Jour G13, Delorenzo M14, Martin AM15, Levy A16, Dalvi N17, Hansford JR18, Gottardo NG19, Uro-Coste E20, Maurage CA21, Godfraind C22, Vandenbos F23, Pietsch T24, Kramm C25, Filippidou M26, Kattamis A27, Jones C28, Øra I29, Mikkelsen TS30, Zapotocky M31, Sumerauer D32, Scheie D33, McCabe M34, Wesseling P35, Tops BBJ36, Kranendonk MEG37, Karajannis MA38, Bouvier N39, Papaemmanuil E40, Dohmen H41, Acker T42, von Hoff K43, Schmid S44, Miele E45, Filipski K46, Kitanovski L47, Krskova L48, Gojo J49, Haberler C50, Alvaro F51, Ecker J52, Selt F53, Milde T54, Witt O55, Oehme I56, Kool M57, von Deimling A58, Korshunov A59, Pfister SM60, Sahm F61, Jones DTW62 |
 Author information
|
|
Abstract Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens. |
|
© 2021. The Author(s). |
|
KEYWORDS: Brain tumor, EWSR1, Gene fusion, MN1, Neuroepithelial, Neurooncology, PATZ1, Pediatric |
|
Publikations ID: 34417833 Quelle: öffnen |
Author information
Schnellinfo
-- Cancer Care
-- Kliniken und Partner
-- CCC Cancer School
-- Young CCC
-- CCC Tumorboards
-- CCC Forschungscluster
-- CCC Units
-- CCC Platforms
-- SOPs / Leitlinien
-- Kontakt
Featured
