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PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum
KT. Alhalabi, D. Stichel, P. Sievers, H. Peterziel, AC. Sommerkamp, D. Sturm, A. Wittmann, M. Sill, N. Jäger, P. Beck, KW. Pajtler, M. Snuderl, G. Jour, M. Delorenzo, AM. Martin, A. Levy, N. Dalvi, JR. Hansford, NG. Gottardo, E. Uro-Coste, CA....
Language English Country Germany
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
P30 CA008748
NCI NIH HHS - United States
P50 HD105352
NICHD NIH HHS - United States
NLK
ProQuest Central
from 1997-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 1997-01-01 to 1 year ago
Psychology Database (ProQuest)
from 1997-01-01 to 1 year ago
- MeSH
- Child MeSH
- Oncogene Proteins, Fusion genetics MeSH
- Humans MeSH
- Biomarkers, Tumor genetics MeSH
- Brain Neoplasms genetics pathology MeSH
- Neoplasms, Neuroepithelial genetics pathology MeSH
- Oncogene Fusion MeSH
- Child, Preschool MeSH
- Repressor Proteins genetics MeSH
- Kruppel-Like Transcription Factors genetics MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
Center for Hematologic Malignancies Memorial Sloan Kettering Cancer Center New York NY USA
Children's Hospital Paediatric Oncology Skåne University Hospital Lund Sweden
Department of Clinical Medicine Rigshospitalet University of Copenhagen Copenhagen Denmark
Department of Neuropathology Heidelberg University Hospital Heidelberg Germany
Department of Neuropathology University Giessen Giessen Germany
Department of Oncology and Haematology Perth Children's Hospital Perth WA Australia
Department of Pathology CHU Gabriel Montpied Clermont Ferrand France
Department of Pathology IUCT Oncopole Toulouse University Hospital Toulouse France
Department of Pathology Lille University Hospital Lille France
Department of Pathology NYU Langone Health New York NY USA
Department of Pediatrics Albert Einstein College of Medicine Bronx New York USA
Department of Pediatrics Memorial Sloan Kettering Cancer Center New York USA
Division of Cancer Sciences University of Manchester Manchester UK
Division of Molecular Pathology Institute of Cancer Research London UK
Division of Neuropathology NYU Langone Health New York NY USA
Division of Pediatric Glioma Research Im Neuenheimer Feld 280 69120 Heidelberg Germany
Division of Pediatric Hematology and Oncology University Medical Center Göttingen Gottingen Germany
Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany
Faculty of Medicine Heidelberg University Heidelberg Germany
Frankfurt Cancer Institute Frankfurt Germany
German Cancer Consortium Heidelberg Germany
Hopp Children's Cancer Center Heidelberg Heidelberg Germany
Human Molecular Genetics de Duve Institute Université Catholique de Louvain Brussels Belgium
INSERM U1037 Team 11 Cancer Research Center of Toulouse Toulouse France
INSERM U837 UMR S1172 Centre de Recherche Jean Pierre Aubert Team 1 Lille France
Isabel Rapin Division of Child Neurology Albert Einstein College of Medicine Bronx New York USA
John Hunter Children's Hospital Newcastle Newcastle NSW Australia
Laboratory of Pathology University Hospital of Clermont Ferrand Clermont Ferrand France
Neurological Institute University Hospital Frankfurt Germany
Princess Maxima Center for Pediatric Oncology Utrecht The Netherlands
University Clermont Auvergne M2iSH UMR1071 Clermont Ferrand France
References provided by Crossref.org
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