@article{2997013,
    title = "PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum",
    author = "Alhalabi, K.T. and Stichel, D. and Sievers, P. and Peterziel, H. and Sommerkamp, A.C. and Sturm, D. and Wittmann, A. and Sill, M. and Jäger, N. and Beck, P. and Pajtler, K.W. and Snuderl, M. and Jour, G. and Delorenzo, M. and Martin, A.M. and Levy, A. and Dalvi, N. and Hansford, J.R. and Gottardo, N.G. and Uro-Coste, E. and Maurage, C.-A. and Godfraind, C. and Vandenbos, F. and Pietsch, T. and Kramm, C. and Filippidou, M. and Kattamis, A. and Jones, C. and Øra, I. and Mikkelsen, T.S. and Zapotocky, M. and Sumerauer, D. and Scheie, D. and McCabe, M. and Wesseling, P. and Tops, B.B.J. and Kranendonk, M.E.G. and Karajannis, M.A. and Bouvier, N. and Papaemmanuil, E. and Dohmen, H. and Acker, T. and von Hoff, K. and Schmid, S. and Miele, E. and Filipski, K. and Kitanovski, L. and Krskova, L. and Gojo, J. and Haberler, C. and Alvaro, F. and Ecker, J. and Selt, F. and Milde, T. and Witt, O. and Oehme, I. and Kool, M. and von Deimling, A. and Korshunov, A. and Pfister, S.M. and Sahm, F. and Jones, D.T.W.",
    journal = "Acta Neuropathologica",
    year = "2021",
    volume = "142",
    number = "5",
    pages = "841-857",
    publisher = "Springer Science and Business Media Deutschland GmbH",
    issn = "0001-6322, 1432-0533",
    doi = "10.1007/s00401-021-02354-8",
    keywords = "antineoplastic agent;  B Raf kinase;  cald1 protein;  CD34 antigen;  CD99 antigen;  desmin;  ewsr1 patz1 fusion protein;  fusion protein;  glial fibrillary acidic protein;  h3f3a protein;  isocitrate dehydrogenase 1;  isocitrate dehydrogenase 2;  Ki 67 antigen;  messenger RNA;  microtubule associated protein 2;  mn1 patz1 fusion protein;  MyoD1 protein;  myogenin;  neuron specific nuclear protein;  oligodendrocyte transcription factor 2;  protein;  protein p53;  protein S 100;  somatomedin B;  synaptophysin;  transcription factor GATA 2;  transcription factor PAX2;  transcription factor Sox10;  unclassified drug;  vimentin;  kruppel like factor;  oncoprotein;  PATZ1 protein, human;  repressor protein;  tumor marker, adult;  Article;  brain histology;  brain tumor cell line;  cancer prognosis;  cancer recurrence;  central nervous system tumor;  chromosome 22;  clinical study;  cohort analysis;  controlled study;  copy number variation;  cytoplasm;  differential expression analysis;  DNA methylation;  drug screening;  dysembryoplastic neuroepithelial tumor;  Ewing sarcoma;  glioblastoma;  glioma;  histopathology;  human;  human cell;  human tissue;  immunohistochemistry;  major clinical study;  middle aged;  molecular fingerprinting;  neuroblastoma;  neuroepithelioma;  pilocytic astrocytoma;  pleomorphic xanthoastrocytoma;  reference database;  RNA sequencing;  sarcoma;  small cell sarcoma;  subependymal giant cell astrocytoma;  whole exome sequencing;  brain tumor;  child;  female;  gene fusion;  genetics;  male;  neuroepithelioma;  pathology;  preschool child, Biomarkers, Tumor;  Brain Neoplasms;  Child;  Child, Preschool;  Female;  Humans;  Kruppel-Like Transcription Factors;  Male;  Neoplasms, Neuroepithelial;  Oncogene Fusion;  Oncogene Proteins, Fusion;  Repressor Proteins",
    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)."
}