PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum
Authors
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, Martin G
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.
Affiliation
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, GermanyIssue Date
2021
Metadata
Show full item recordAbstract
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.Citation
Alhalabi KT, Stichel D, Sievers P, Peterziel H, Sommerkamp AC, Sturm D, et al. PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum. Acta Neuropathol. 2021 Aug 21.Journal
Acta NeuropathologicaDOI
10.1007/s00401-021-02354-8PubMed ID
34417833Additional Links
https://dx.doi.org/10.1007/s00401-021-02354-8Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1007/s00401-021-02354-8
Scopus Count
Collections
Related articles
- A novel LARGE1-AFF2 fusion expanding the molecular alterations associated with the methylation class of neuroepithelial tumors with PATZ1 fusions.
- Authors: Tauziède-Espariat A, Chotard G, le Loarer F, Baud J, Azmani R, Dangouloff-Ros V, Boddaert N, Icher-de-Bouyn C, Gimbert E, Hasty L, Métais A, Chrétien F, Varlet P, the RENOCLIP-LOC
- Issue date: 2022 Feb 3
- EWSR1-PATZ1 gene fusion may define a new glioneuronal tumor entity.
- Authors: Siegfried A, Rousseau A, Maurage CA, Pericart S, Nicaise Y, Escudie F, Grand D, Delrieu A, Gomez-Brouchet A, Le Guellec S, Franchet C, Boetto S, Vinchon M, Sol JC, Roux FE, Rigau V, Bertozzi AI, Jones DTW, Figarella-Branger D, Uro-Coste E
- Issue date: 2019 Jan
- A polyphenotypic malignant paediatric brain tumour presenting a MN1-PATZ1 fusion, no epigenetic similarities with CNS High-Grade Neuroepithelial Tumour with MN1 Alteration (CNS HGNET-MN1) and related to PATZ1-fused sarcomas.
- Authors: Burel-Vandenbos F, Pierron G, Thomas C, Reynaud S, Gregoire V, Duhil de Benaze G, Croze S, Chivoret N, Honavar M, Figarella-Branger D, Maurage CA, Pedeutour F, Hasselblatt M, Godfraind C
- Issue date: 2020 Aug
- A rare case of paediatric astroblastoma with concomitant MN1-GTSE1 and EWSR1-PATZ1 gene fusions altering management.
- Authors: Chadda KR, Holland K, Scoffings D, Dean A, Pickles JC, Behjati S, Jacques TS, Trotman J, Tarpey P, Allinson K, Murray MJ, Genomics England Research Consortium
- Issue date: 2021 Oct
- The spectrum of rare central nervous system (CNS) tumors with EWSR1-non-ETS fusions: experience from three pediatric institutions with review of the literature.
- Authors: Lopez-Nunez O, Cafferata B, Santi M, Ranganathan S, Pearce TM, Kulich SM, Bailey KM, Broniscer A, Rossi S, Zin A, Nasrallah MP, Li MM, Zhong Y, Miele E, Alaggio R, Surrey LF
- Issue date: 2021 Jan