Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1.

Brain Neoplasms / genetics Chromosomes, Human, Pair 1 / genetics Chromosomes, Human, Pair 7 / genetics Cohort Studies Cyclin-Dependent Kinase Inhibitor p16 / genetics DNA Copy Number Variations DNA Methylation Female Gene Deletion Glial Fibrillary Acidic Protein / biosynthesis Glioblastoma / genetics Humans Male Middle Aged Neuroectodermal Tumors, Primitive / genetics PTEN Phosphohydrolase / genetics Retinoblastoma Binding Proteins / genetics Tumor Suppressor Protein p53 / genetics Ubiquitin-Protein Ligases / genetics
Classification DNA methylation GBM PNET Phenotype Plasticity

Journal

Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041

Informations de publication

Date de publication:
07 2021
Historique:
received: 18 02 2021
accepted: 26 03 2021
revised: 24 03 2021
pubmed: 21 4 2021
medline: 11 1 2022
entrez: 20 4 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1007/s00401-021-02302-6 PMID: 33876327 PMC: PMC8217054
pubmed: 33876327
doi: 10.1007/s00401-021-02302-6
pii: 10.1007/s00401-021-02302-6
pmc: PMC8217054
doi:

Substances chimiques

CDKN2A protein, human 0
Cyclin-Dependent Kinase Inhibitor p16 0
GFAP protein, human 0
Glial Fibrillary Acidic Protein 0
RB1 protein, human 0
Retinoblastoma Binding Proteins 0
TP53 protein, human 0
Tumor Suppressor Protein p53 0
Ubiquitin-Protein Ligases EC 2.3.2.27
PTEN Phosphohydrolase EC 3.1.3.67
PTEN protein, human EC 3.1.3.67

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

179-189

Subventions

Organisme : Medical Research Council
ID : G0701018
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1100578
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N004272/1
Pays : United Kingdom

Références

Balanis NG, Sheu KM, Esedebe FN, Patel SJ, Smith BA, Park JW, et al. (2019) Pan-cancer convergence to a small-cell neuroendocrine phenotype that shares susceptibilities with hematological malignancies. Cancer Cell 36:17-34.e17. https://doi.org/10.1016/j.ccell.2019.06.005
doi: 10.1016/j.ccell.2019.06.005 pubmed: 31287989 pmcid: 6703903
Bieging KT, Mello SS, Attardi LD (2014) Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer 14:359–370. https://doi.org/10.1038/nrc3711
doi: 10.1038/nrc3711 pubmed: 24739573 pmcid: 4049238
Bingle CD (1997) Thyroid transcription factor-1. Int J Biochem Cell Biol 29:1471–1473. https://doi.org/10.1016/s1357-2725(97)00007-1
doi: 10.1016/s1357-2725(97)00007-1 pubmed: 9570141
Brat DJ, Aldape K, Colman H, Holland EC, Louis DN, Jenkins RB, et al. (2018) cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV.” Acta Neuropathol 136:805–810. https://doi.org/10.1007/s00401-018-1913-0
doi: 10.1007/s00401-018-1913-0 pubmed: 30259105 pmcid: 6204285
Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, et al. (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469–474. https://doi.org/10.1038/nature26000
doi: 10.1038/nature26000 pubmed: 29539639 pmcid: 6093218
Capper D, Stichel D, Sahm F, Jones DTW, Schrimpf D, Sill M, et al. (2018) Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. Acta Neuropathol 136:181–210. https://doi.org/10.1007/s00401-018-1879-y
doi: 10.1007/s00401-018-1879-y pubmed: 29967940 pmcid: 6060790
Comprehensive genomic characterization defines human glioblastoma genes and core pathways (2008). Nature 455:1061–1068. https://doi.org/10.1038/nature07385
Euskirchen P, Bielle F, Labreche K, Kloosterman WP, Rosenberg S, Daniau M, et al. (2017) Same-day genomic and epigenomic diagnosis of brain tumors using real-time nanopore sequencing. Acta Neuropathol 134:691–703. https://doi.org/10.1007/s00401-017-1743-5
doi: 10.1007/s00401-017-1743-5 pubmed: 28638988 pmcid: 5645447
Galloway M, Sim R (2007) TTF-1 staining in glioblastoma multiforme. Virchows Arch 451:109–111. https://doi.org/10.1007/s00428-007-0432-5
doi: 10.1007/s00428-007-0432-5 pubmed: 17562073
Henriquez NV, Forshew T, Tatevossian R, Ellis M, Richard-Loendt A, Rogers H, et al. (2013) Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro. Cancer Res 73:5834–5844. https://doi.org/10.1158/0008-5472.Can-13-1299
doi: 10.1158/0008-5472.Can-13-1299 pubmed: 23887970
Jacques TS, Swales A, Brzozowski MJ, Henriquez NV, Linehan JM, Mirzadeh Z, et al. (2010) Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes. Embo J 29:222–235. https://doi.org/10.1038/emboj.2009.327
doi: 10.1038/emboj.2009.327 pubmed: 19927122
Kaplan KJ, Perry A (2007) Gliosarcoma with primitive neuroectodermal differentiation: case report and review of the literature. J Neurooncol 83:313–318. https://doi.org/10.1007/s11060-007-9331-5
doi: 10.1007/s11060-007-9331-5 pubmed: 17406789
Kastenhuber ER, Lowe SW (2017) Putting p53 in context. Cell 170:1062–1078. https://doi.org/10.1016/j.cell.2017.08.028
doi: 10.1016/j.cell.2017.08.028 pubmed: 28886379 pmcid: 5743327
Kepes JJ (2002) Gliosarcoma with areas of primitive neuroepithelial differentiation and extracranial metastasis. Clin Neuropathol 21:193–195 (author reply 195-196)
pubmed: 12143929
Koshy M, Villano JL, Dolecek TA, Howard A, Mahmood U, Chmura SJ, et al. (2012) Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neurooncol 107:207–212. https://doi.org/10.1007/s11060-011-0738-7
doi: 10.1007/s11060-011-0738-7 pubmed: 21984115
Lazzaro D, Price M, de Felice M, Di Lauro R (1991) The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Development (Cambridge, England) 113:1093–1104
doi: 10.1242/dev.113.4.1093
Li Y, Nichols MA, Shay JW, Xiong Y (1994) Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb. Can Res 54:6078–6082
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. (2016) The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820. https://doi.org/10.1007/s00401-016-1545-1
doi: 10.1007/s00401-016-1545-1 pubmed: 27157931
Mandel JJ, Yust-Katz S, Cachia D, Wu J, Liu D, de Groot JF, et al. (2014) Leptomeningeal dissemination in glioblastoma; an inspection of risk factors, treatment, and outcomes at a single institution. J Neurooncol 120:597–605. https://doi.org/10.1007/s11060-014-1592-1
doi: 10.1007/s11060-014-1592-1 pubmed: 25168214
Neftel C, Laffy J, Filbin MG, Hara T, Shore ME, Rahme GJ, et al. (2019) An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell 178:835-849.e821. https://doi.org/10.1016/j.cell.2019.06.024
doi: 10.1016/j.cell.2019.06.024 pubmed: 31327527 pmcid: 6703186
Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J, Ehrenberger T, et al. (2017) The whole-genome landscape of medulloblastoma subtypes. Nature 547:311–317. https://doi.org/10.1038/nature22973
doi: 10.1038/nature22973 pubmed: 28726821 pmcid: 5905700
Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, et al. (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522. https://doi.org/10.1016/j.ccr.2010.03.017
doi: 10.1016/j.ccr.2010.03.017 pubmed: 20399149 pmcid: 2872684
Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS (2020) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013–2017. Neuro-Oncol 22:iv1–iv96. https://doi.org/10.1093/neuonc/noaa200
doi: 10.1093/neuonc/noaa200 pubmed: 33123732
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812. https://doi.org/10.1126/science.1164382
doi: 10.1126/science.1164382 pubmed: 18772396 pmcid: 2820389
Perry A, Miller CR, Gujrati M, Scheithauer BW, Zambrano SC, Jost SC, et al. (2009) Malignant gliomas with primitive neuroectodermal tumor-like components: a clinicopathologic and genetic study of 53 cases. Brain Pathol 19:81–90. https://doi.org/10.1111/j.1750-3639.2008.00167.x
doi: 10.1111/j.1750-3639.2008.00167.x pubmed: 18452568
Rayess H, Wang MB, Srivatsan ES (2012) Cellular senescence and tumor suppressor gene p16. Int J Cancer 130:1715–1725. https://doi.org/10.1002/ijc.27316
doi: 10.1002/ijc.27316 pubmed: 22025288
Reuss DE, Sahm F, Schrimpf D, Wiestler B, Capper D, Koelsche C, et al. (2015) ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 129:133–146. https://doi.org/10.1007/s00401-014-1370-3
doi: 10.1007/s00401-014-1370-3 pubmed: 25427834
Sahm F, Schrimpf D, Jones DT, Meyer J, Kratz A, Reuss D, et al. (2016) Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets. Acta Neuropathol 131:903–910. https://doi.org/10.1007/s00401-015-1519-8
doi: 10.1007/s00401-015-1519-8 pubmed: 26671409
Sahm F, Schrimpf D, Stichel D, Jones DTW, Hielscher T, Schefzyk S, et al. (2017) DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. Lancet Oncol 18:682–694. https://doi.org/10.1016/s1470-2045(17)30155-9
doi: 10.1016/s1470-2045(17)30155-9 pubmed: 28314689
Shintaku M, Yoneda H, Hirato J, Nagaishi M, Okabe H (2013) Gliosarcoma with ependymal and PNET-like differentiation. Clin Neuropathol 32:508–514. https://doi.org/10.5414/np300624
doi: 10.5414/np300624 pubmed: 23863343
Silbergeld DL, Rostomily RC, Alvord EC Jr (1991) The cause of death in patients with glioblastoma is multifactorial: clinical factors and autopsy findings in 117 cases of supratentorial glioblastoma in adults. J Neurooncol 10:179–185. https://doi.org/10.1007/bf00146880
doi: 10.1007/bf00146880 pubmed: 1654403
Song X, Andrew Allen R, Terence Dunn S, Fung KM, Farmer P, Gandhi S, et al. (2011) Glioblastoma with PNET-like components has a higher frequency of isocitrate dehydrogenase 1 (IDH1) mutation and likely a better prognosis than primary glioblastoma. Int J Clin Exp Pathol 4:651–660
pubmed: 22076165 pmcid: 3209605
Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, et al. (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:425–437. https://doi.org/10.1016/j.ccr.2012.08.024
doi: 10.1016/j.ccr.2012.08.024 pubmed: 23079654
Suvà ML, Tirosh I (2020) The glioma stem cell model in the era of single-cell genomics. Cancer Cell 37:630–636. https://doi.org/10.1016/j.ccell.2020.04.001
doi: 10.1016/j.ccell.2020.04.001 pubmed: 32396858 pmcid: 32396858
Suwala AK, Stichel D, Schrimpf D, Kloor M, Wefers AK, Reinhardt A, et al. (2020) Primary mismatch repair deficient IDH-mutant astrocytoma (PMMRDIA) is a distinct type with a poor prognosis. Acta Neuropathol. https://doi.org/10.1007/s00401-020-02243-6
doi: 10.1007/s00401-020-02243-6 pubmed: 33216206 pmcid: 7785563
Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110. https://doi.org/10.1016/j.ccr.2009.12.020
doi: 10.1016/j.ccr.2009.12.020 pubmed: 20129251 pmcid: 2818769
Watanabe K, Sato K, Biernat W, Tachibana O, von Ammon K, Ogata N, et al. (1997) Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies. Clin Cancer Res: Off J Am Assoc Cancer Res 3:523–530
Xu G, Zheng H, Li JY (2019) Next-generation whole exome sequencing of glioblastoma with a primitive neuronal component. Brain Tumor Pathol 36:129–134. https://doi.org/10.1007/s10014-019-00334-1
doi: 10.1007/s10014-019-00334-1 pubmed: 30715630

Auteurs

Abigail K Suwala (AK)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
Department of Neurological Surgery, Helen Diller Research Center, University of California San Francisco, San Francisco, CA, USA.

Damian Stichel (D)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Daniel Schrimpf (D)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Sybren L N Maas (SLN)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Martin Sill (M)

Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.

Hildegard Dohmen (H)

Institute of Neuropathology, University of Giessen, Giessen, Germany.

Rouzbeh Banan (R)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

Annekathrin Reinhardt (A)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Philipp Sievers (P)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Felix Hinz (F)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Mirjam Blattner-Johnson (M)

Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Christian Hartmann (C)

Department of Neuropathology, Institute of Pathology, Hannover Medical School, Hannover, Germany.

Leonille Schweizer (L)

Department of Neuropathology, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Henning B Boldt (HB)

Department of Pathology, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Bjarne Winther Kristensen (BW)

Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Clinical Medicine and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.

Jens Schittenhelm (J)

Institute of Pathology and Neuropathology, Department of Neuropathology, University Hospital Tübingen, Tübingen, Germany.

Matthew D Wood (MD)

Department of Pathology, Oregon Health and Science University, Portland, OR, USA.

Guillaume Chotard (G)

Department of Pathology, Hospital Center University of Bordeaux, Bordeaux, France.

Rolf Bjergvig (R)

Department of Biomedicine, University of Bergen, Bergen, Norway.

Anirban Das (A)

Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.

Uri Tabori (U)

Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada.
Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Canada.

Martin Hasselblatt (M)

Institute of Neuropathology, University Hospital Münster, Munster, Germany.

Andrey Korshunov (A)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.

Zied Abdullaev (Z)

Laboratory of Pathology, National Cancer Institute Centre for Cancer Research, Bethesda, MD, USA.

Martha Quezado (M)

Laboratory of Pathology, National Cancer Institute Centre for Cancer Research, Bethesda, MD, USA.

Kenneth Aldape (K)

Laboratory of Pathology, National Cancer Institute Centre for Cancer Research, Bethesda, MD, USA.

Patrick N Harter (PN)

Neurological Institute (Edinger Institute), Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany.
German Cancer Research Center (DKFZ), Heidelberg, Germany.

Matija Snuderl (M)

Division of Neuropathology, NYU Langone Health, New York, USA.
Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, USA.
Division of Molecular Pathology and Diagnostics, NYU Langone Health, New York, USA.

Jürgen Hench (J)

Division of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland.

Stephan Frank (S)

Division of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland.

Till Acker (T)

Institute of Neuropathology, University of Giessen, Giessen, Germany.

Sebastian Brandner (S)

Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals, London, UK.
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK.

Frank Winkler (F)

Clinical Cooperation Unit Neurooncology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany.

Pieter Wesseling (P)

Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Department of Pathology, Amsterdam University Medical Centers/VUmc and Brain Tumor Center Amsterdam, Amsterdam, The Netherlands.

Stefan M Pfister (SM)

Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany.

David E Reuss (DE)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Wolfgang Wick (W)

Clinical Cooperation Unit Neurooncology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany.

Andreas von Deimling (A)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

David T W Jones (DTW)

Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Felix Sahm (F)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. Felix.Sahm@med.uni-heidelberg.de.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany. Felix.Sahm@med.uni-heidelberg.de.
Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany. Felix.Sahm@med.uni-heidelberg.de.
ORCID: 0000-0001-5441-1962

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 1-3 › Chromosomes humains de la paire 1 › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 6-12 et X › Chromosomes humains de la paire 7 › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Protéines inhibitrices des kinases cyclines-dépendantes › Inhibiteur p16 de kinase cycline-dépendante › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Phénomènes génétiques › Mutagenèse › Délétion de séquence › Délétion de gène › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines de filaments intermédiaires › Protéine gliofibrillaire acide › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Glioblastome › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Tumeurs neuroectodermiques primitives › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Phosphohydrolase PTEN › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines de liaison à la protéine du rétinoblastome › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › Glioblastomas with primitive neuronal...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Glioblastomas with primitive neuronal...