PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum

Autor: Elli Papaemmanuil, Bastiaan B. J. Tops, Torben Stamm Mikkelsen, Fanny Vandenbos, Christof M. Kramm, Nancy Bouvier, Katharina Filipski, Nagma Dalvi, Kristian W. Pajtler, Andrea Wittmann, Christine Haberler, Till Milde, Olaf Witt, Hildegard Dohmen, Martin Sill, George Jour, Matija Snuderl, Allison M. Martin, Torsten Pietsch, Antonis Kattamis, Nicholas G. Gottardo, Emmanuelle Uro-Coste, Philipp Sievers, Andreas von Deimling, Frank Alvaro, Simone Schmid, Damian Stichel, Jonas Ecker, Marcel Kool, Johannes Gojo, Lidija Kitanovski, Michal Zapotocky, Michael Delorenzo, Catherine Godfraind, Florian Selt, Alexander C Sommerkamp, Adam S. Levy, Pieter Wesseling, Evelina Miele, Lenka Krskova, Pengbo Beck, Matthias A. Karajannis, David Scheie, Jordan R. Hansford, Natalie Jäger, Karam T. Alhalabi, Andrey Korshunov, Felix Sahm, Mariëtte E.G. Kranendonk, David T.W. Jones, David Sumerauer, Chris Jones, Katja von Hoff, Heike Peterziel, Stefan M. Pfister, Dominik Sturm, Martin G. McCabe, Ina Oehme, Maria Filippidou, Claude Alain Maurage, Ingrid Øra, Till Acker
Přispěvatelé: Pathology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Pathology
medicine.medical_specialty
Oncogene Proteins
Fusion
PATZ1
Kruppel-Like Transcription Factors
Brain tumor
Neuroepithelial
Biology
Malignancy
Pathology and Forensic Medicine
Fusion gene
Cellular and Molecular Neuroscience
Biomarkers
Tumor
medicine
Humans
Oncogene Fusion
Copy-number variation
ddc:610
Child
Kruppel-Like Transcription Factors/genetics
Brain Neoplasms/genetics
Pediatric
Neoplasms
Neuroepithelial/genetics
Repressor Proteins/genetics
Original Paper
Manchester Cancer Research Centre
MN1
Brain Neoplasms
ResearchInstitutes_Networks_Beacons/mcrc
GATA2
Neurooncology
medicine.disease
Neoplasms
Neuroepithelial
Repressor Proteins
Neuroepithelial cell
EWSR1
Child
Preschool
Oncogene Proteins
Fusion/genetics
Female
Neurology (clinical)
Biomarkers
Tumor/genetics
Chromosome 22
Gene fusion
Zdroj: Alhalabi, K T, Stichel, D, Sievers, P, Peterziel, H, Sommerkamp, A C, Sturm, D, Wittmann, A, Sill, M, Jäger, N, Beck, P, Pajtler, K W, Snuderl, M, Jour, G, Delorenzo, M, Martin, A M, Levy, A, Dalvi, N, Hansford, J R, Gottardo, N G, Uro-Coste, E, Maurage, C A, Godfraind, C, Vandenbos, F, Pietsch, T, Kramm, C, Filippidou, M, Kattamis, A, Jones, C, Øra, I, Mikkelsen, T S, Zapotocky, M, Sumerauer, D, Scheie, D, McCabe, M, Wesseling, P, Tops, B B J, Kranendonk, M E G, Karajannis, M A, Bouvier, N, Papaemmanuil, E, Dohmen, H, Acker, T, von Hoff, K, Schmid, S, Miele, E, Filipski, K, Kitanovski, L, Krskova, L, Gojo, J, Haberler, C, Alvaro, F, Ecker, J, Selt, F, Milde, T, Witt, O, Oehme, I, Kool, M, von Deimling, A, Korshunov, A, Pfister, S M, Sahm, F & Jones, D T W 2021, ' PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum ', Acta Neuropathologica, vol. 142, no. 5, pp. 841-857 . https://doi.org/10.1007/s00401-021-02354-8
Acta Neuropathologica
Alhalabi, K T, Stichel, D, Sievers, P, Peterziel, H, Sommerkamp, A C, Sturm, D, Wittmann, A, Sill, M, Jäger, N, Beck, P, Pajtler, K W, Snuderl, M, Jour, G, Delorenzo, M, Martin, A M, Levy, A, Dalvi, N, Hansford, J R, Gottardo, N G, Uro-Coste, E, Maurage, C-A, Godfraind, C, Vandenbos, F, Pietsch, T, Kramm, C, Filippidou, M, Kattamis, A, Øra, I, Mikkelsen, T S, Zapotocky, M, Sumerauer, D, Scheie, D, McCabe, M, Wesseling, P, Tops, B B J, Kranendonk, M E G, Karajannis, M A, Bouvier, N, Papaemmanuil, E, Dohmen, H, Acker, T, von Hoff, K, Schmid, S, Miele, E, Filipski, K, Kitanovski, L, Krskova, L, Gojo, J, Haberler, C, Alvaro, F, Ecker, J, Selt, F, Milde, T, Witt, O, Oehme, I, Kool, M, von Deimling, A, Korshunov, A, Pfister, S M & Sahm, F 2021, ' PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum ', Acta Neuropathologica, vol. 142, no. 5, pp. 841-857 . https://doi.org/10.1007/s00401-021-02354-8
Alhalabi, K T, Stichel, D, Sievers, P, Peterziel, H, Sommerkamp, A C, Sturm, D, Wittmann, A, Sill, M, Jäger, N, Beck, P, Pajtler, K W, Snuderl, M, Jour, G, Delorenzo, M, Martin, A M, Levy, A, Dalvi, N, Hansford, J R, Gottardo, N G, Uro-Coste, E, Maurage, C-A, Godfraind, C, Vandenbos, F, Pietsch, T, Kramm, C, Filippidou, M, Kattamis, A, Jones, C, Øra, I, Mikkelsen, T S, Zapotocky, M, Sumerauer, D, Scheie, D, McCabe, M, Wesseling, P, Tops, B B J, Kranendonk, M E G, Karajannis, M A, Bouvier, N, Papaemmanuil, E, Dohmen, H, Acker, T, von Hoff, K, Schmid, S, Miele, E, Filipski, K, Kitanovski, L, Krskova, L, Gojo, J, Haberler, C, Alvaro, F, Ecker, J, Selt, F, Milde, T, Witt, O, Oehme, I, Kool, M, von Deimling, A, Korshunov, A, Pfister, S M, Sahm, F & Jones, D T W 2021, ' PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum ', Acta Neuropathologica, vol. 142, no. 5, pp. 841-857 . https://doi.org/10.1007/s00401-021-02354-8
Alhalabi, K T, Stichel, D, Sievers, P, Peterziel, H, Sommerkamp, A C, Sturm, D, Wittmann, A, Sill, M, Jäger, N, Beck, P, Pajtler, K W, Snuderl, M, Jour, G, Delorenzo, M, Martin, A M, Levy, A, Dalvi, N, Hansford, J R, Gottardo, N G, Uro-Coste, E, Maurage, C A, Godfraind, C, Vandenbos, F, Pietsch, T, Kramm, C, Filippidou, M, Kattamis, A, Jones, C, Øra, I, Mikkelsen, T S, Zapotocky, M, Sumerauer, D, Scheie, D, McCabe, M, Wesseling, P, Tops, B B J, Kranendonk, M E G, Karajannis, M A, Bouvier, N, Papaemmanuil, E, Dohmen, H, Acker, T, von Hoff, K, Schmid, S, Miele, E, Filipski, K, Kitanovski, L, Krskova, L, Gojo, J, Haberler, C, Alvaro, F, Ecker, J, Selt, F, Milde, T, Witt, O, Oehme, I, Kool, M, von Deimling, A, Korshunov, A, Pfister, S M, Sahm, F & Jones, D T W 2021, ' PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum ', Acta Neuropathologica, vol. 142, pp. 841–857 . https://doi.org/10.1007/s00401-021-02354-8
Acta Neuropathologica, 142(5), 841-857. Springer Verlag
ISSN: 0001-6322
DOI: 10.1007/s00401-021-02354-8
Popis: 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.
Databáze: OpenAIRE
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