Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1
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| Titel: | Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1 |
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| Autoren: | Martin Hasselblatt, Till Acker, Christian Hartmann, Matija Snuderl, Leonille Schweizer, Uri Tabori, Patrick N. Harter, Martin Sill, David T.W. Jones, Felix Sahm, Anirban Das, Mirjam Blattner-Johnson, Jens Schittenhelm, Pieter Wesseling, Zied Abdullaev, Abigail K. Suwala, Philipp Sievers, Matthew D. Wood, Andreas von Deimling, Sebastian Brandner, Henning B. Boldt, Stefan M. Pfister, Guillaume Chotard, Felix Hinz, Jürgen Hench, Frank Winkler, Wolfgang Wick, Martha Quezado, Annekathrin Reinhardt, David E. Reuss, Rolf Bjergvig, Sybren L. N. Maas, Kenneth Aldape, Stephan Frank, Daniel Schrimpf, Hildegard Dohmen, Andrey Korshunov, Bjarne Winther Kristensen, Damian Stichel, Rouzbeh Banan |
| Weitere Verfasser: | Pathologie Opleiding, Cancer |
| Quelle: | Acta Neuropathol Acta Neuropathologica Suwala, A K, Stichel, D, Schrimpf, D, Maas, S L N, Sill, M, Dohmen, H, Banan, R, Reinhardt, A, Sievers, P, Hinz, F, Blattner-Johnson, M, Hartmann, C, Schweizer, L, Boldt, H B, Kristensen, B W, Schittenhelm, J, Wood, M D, Chotard, G, Bjergvig, R, Das, A, Tabori, U, Hasselblatt, M, Korshunov, A, Abdullaev, Z, Quezado, M, Aldape, K, Harter, P N, Snuderl, M, Hench, J R, Frank, S, Acker, T, Brandner, S, Winkler, F, Wesseling, P, Pfister, S M, Reuss, D E, Wick, W, von Deimling, A, Jones, D T W & Sahm, F 2021, 'Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1', Acta Neuropathologica, vol. 142, no. 1, pp. 179-189. https://doi.org/10.1007/s00401-021-02302-6 Suwala, A K, Stichel, D, Schrimpf, D, Maas, S L N, Sill, M, Dohmen, H, Banan, R, Reinhardt, A, Sievers, P, Hinz, F, Blattner-johnson, M, Hartmann, C, Schweizer, L, Boldt, H B, Kristensen, B W, Schittenhelm, J, Wood, M D, Chotard, G, Bjergvig, R, Das, A, Tabori, U, Hasselblatt, M, Korshunov, A, Abdullaev, Z, Quezado, M, Aldape, K, Harter, P N, Snuderl, M, Hench, J, Frank, S, Acker, T, Brandner, S, Winkler, F, Wesseling, P, Pfister, S M, Reuss, D E, Wick, W, Von Deimling, A, Jones, D T W & Sahm, F 2021, ' Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1 ', Acta Neuropathologica, vol. 142, pp. 179–189 . https://doi.org/10.1007/s00401-021-02302-6 Suwala, A K, Stichel, D, Schrimpf, D, Maas, S L N, Sill, M, Dohmen, H, Banan, R, Reinhardt, A, Sievers, P, Hinz, F, Blattner-Johnson, M, Hartmann, C, Schweizer, L, Boldt, H B, Kristensen, B W, Schittenhelm, J, Wood, M D, Chotard, G, Bjergvig, R, Das, A, Tabori, U, Hasselblatt, M, Korshunov, A, Abdullaev, Z, Quezado, M, Aldape, K, Harter, P N, Snuderl, M, Hench, J, Frank, S, Acker, T, Brandner, S, Winkler, F, Wesseling, P, Pfister, S M, Reuss, D E, Wick, W, von Deimling, A, Jones, D T W & Sahm, F 2021, ' Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1 ', Acta Neuropathologica, vol. 142, no. 1, pp. 179-189 . https://doi.org/10.1007/s00401-021-02302-6 Acta Neuropathologica, vol 142, iss 1 |
| Verlagsinformationen: | Springer Science and Business Media LLC, 2021. |
| Publikationsjahr: | 2021 |
| Schlagwörter: | Male, 0301 basic medicine, PNET, Neuroectodermal Tumors, Cohort Studies, Primitive, 2.1 Biological and endogenous factors, Neuroectodermal Tumors, Primitive, Aetiology, 10. No inequality, Cancer, 2. Zero hunger, 0303 health sciences, DNA methylation, Brain Neoplasms, Research Support, Non-U.S. Gov't, Ubiquitin-Protein Ligases/genetics [MeSH], Glial Fibrillary Acidic Protein/biosynthesis [MeSH], Glioblastoma/pathology [MeSH], Cohort Studies [MeSH], Neuroectodermal Tumors, Primitive/genetics [MeSH], Male [MeSH], Retinoblastoma Binding Proteins/genetics [MeSH], Glioblastoma/genetics [MeSH], Gene Deletion [MeSH], Female [MeSH], Neuroectodermal Tumors, Primitive/pathology [MeSH], Phenotype, Brain Neoplasms/genetics [MeSH], GBM, Classification, Humans [MeSH], PTEN Phosphohydrolase/genetics [MeSH], Chromosomes, Human, Pair 7/genetics [MeSH], Middle Aged [MeSH], Glial Fibrillary Acidic Protein/genetics [MeSH], Tumor Suppressor Protein p53/genetics [MeSH], Cyclin-Dependent Kinase Inhibitor p16/genetics [MeSH], DNA Copy Number Variations [MeSH], DNA Methylation [MeSH], Plasticity, Original Paper, Chromosomes, Human, Pair 1/genetics [MeSH], Brain Neoplasms/pathology [MeSH], Middle Aged, Retinoblastoma Binding Proteins, Chromosomes, Human, Pair 1, Pair 1, Pair 7, Female, Chromosomes, Human, Pair 7, Human, DNA Copy Number Variations, Ubiquitin-Protein Ligases, Clinical Sciences, Oncology and Carcinogenesis, Clinical Neurology, Chromosomes, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, 03 medical and health sciences, Rare Diseases, Glial Fibrillary Acidic Protein, Genetics, Journal Article, Humans, Cyclin-Dependent Kinase Inhibitor p16, Neurology & Neurosurgery, Biomedical and Clinical Sciences, Human Genome, Neurosciences, PTEN Phosphohydrolase, DNA Methylation, Brain Disorders, Brain Cancer, Tumor Suppressor Protein p53, Glioblastoma, Gene Deletion |
| Beschreibung: | Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature. |
| Publikationsart: | Article Other literature type |
| Dateibeschreibung: | application/pdf |
| Sprache: | English |
| ISSN: | 1432-0533 0001-6322 |
| DOI: | 10.1007/s00401-021-02302-6 |
| Zugangs-URL: | https://link.springer.com/content/pdf/10.1007/s00401-021-02302-6.pdf https://pubmed.ncbi.nlm.nih.gov/33876327 https://pubmed.ncbi.nlm.nih.gov/33876327/ http://europepmc.org/article/MED/33876327 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217054 https://link.springer.com/content/pdf/10.1007/s00401-021-02302-6.pdf https://portal.findresearcher.sdu.dk/en/publications/glioblastomas-with-primitive-neuronal-component-harbor-a-distinct https://research.vumc.nl/en/publications/glioblastomas-with-primitive-neuronal-component-harbor-a-distinct https://hdl.handle.net/11250/2838416 https://research.vumc.nl/en/publications/b19cce4f-5688-4146-bc50-f67a1dcb96da https://dspace.library.uu.nl/handle/1874/443255 https://curis.ku.dk/ws/files/275993976/Suwala2021_Article_GlioblastomasWithPrimitiveNeur.pdf https://portal.findresearcher.sdu.dk/da/publications/790ecb5e-6834-457e-ab0c-54e543e63689 https://doi.org/10.1007/s00401-021-02302-6 https://findresearcher.sdu.dk:8443/ws/files/184340978/Suwala2021_Article_GlioblastomasWithPrimitiveNeur.pdf https://repository.publisso.de/resource/frl:6450722 https://discovery-pp.ucl.ac.uk/id/eprint/10130401/ https://escholarship.org/content/qt2kz927r8/qt2kz927r8.pdf https://escholarship.org/uc/item/2kz927r8 |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . |
| Dokumentencode: | edsair.doi.dedup.....5f81b052a44e1aaaf9d4e681768c874d |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature. |
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| ISSN: | 14320533 00016322 |
| DOI: | 10.1007/s00401-021-02302-6 |