TY - JOUR
TI - PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum
AU - Alhalabi, K.T.
AU - Stichel, D.
AU - Sievers, P.
AU - Peterziel, H.
AU - Sommerkamp, A.C.
AU - Sturm, D.
AU - Wittmann, A.
AU - Sill, M.
AU - Jäger, N.
AU - Beck, P.
AU - Pajtler, K.W.
AU - Snuderl, M.
AU - Jour, G.
AU - Delorenzo, M.
AU - Martin, A.M.
AU - Levy, A.
AU - Dalvi, N.
AU - Hansford, J.R.
AU - Gottardo, N.G.
AU - Uro-Coste, E.
AU - Maurage, C.-A.
AU - Godfraind, C.
AU - Vandenbos, F.
AU - Pietsch, T.
AU - Kramm, C.
AU - Filippidou, M.
AU - Kattamis, A.
AU - Jones, C.
AU - Øra, I.
AU - Mikkelsen, T.S.
AU - Zapotocky, M.
AU - Sumerauer, D.
AU - Scheie, D.
AU - McCabe, M.
AU - Wesseling, P.
AU - Tops, B.B.J.
AU - Kranendonk, M.E.G.
AU - Karajannis, M.A.
AU - Bouvier, N.
AU - Papaemmanuil, E.
AU - Dohmen, H.
AU - Acker, T.
AU - von Hoff, K.
AU - Schmid, S.
AU - Miele, E.
AU - Filipski, K.
AU - Kitanovski, L.
AU - Krskova, L.
AU - Gojo, J.
AU - Haberler, C.
AU - Alvaro, F.
AU - Ecker, J.
AU - Selt, F.
AU - Milde, T.
AU - Witt, O.
AU - Oehme, I.
AU - Kool, M.
AU - von Deimling, A.
AU - Korshunov, A.
AU - Pfister, S.M.
AU - Sahm, F.
AU - Jones, D.T.W.
JO - Acta Neuropathologica
PY - 2021
VL - 142
TODO - 5
SP - 841-857
PB - Springer Science and Business Media Deutschland GmbH
SN - 0001-6322, 1432-0533
TODO - 10.1007/s00401-021-02354-8
TODO - 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
TODO - 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).
ER -