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| Verfasst von: | Mynarek, Martin [VerfasserIn]  |
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| | Obrecht-Sturm, Denise [VerfasserIn] |
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| | Sill, Martin [VerfasserIn] |
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| | Sturm, Dominik [VerfasserIn] |
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| | Kloth-Stachnau, Katja [VerfasserIn] |
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| | Selt, Florian [VerfasserIn] |
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| | Ecker, Jonas [VerfasserIn] |
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| | Hoff, Katja von [VerfasserIn] |
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| | Juhnke, Björn-Ole [VerfasserIn] |
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| | Goschzik, Tobias [VerfasserIn] |
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| | Pietsch, Torsten [VerfasserIn] |
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| | Bockmayr, Michael [VerfasserIn] |
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| | Kool, Marcel [VerfasserIn] |
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| | Deimling, Andreas von [VerfasserIn] |
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| | Witt, Olaf [VerfasserIn] |
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| | Schüller, Ulrich [VerfasserIn] |
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| | Benesch, Martin [VerfasserIn] |
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| | Gerber, Nicolas U. [VerfasserIn] |
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| | Sahm, Felix [VerfasserIn] |
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| | Jones, David T. W. [VerfasserIn] |
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| | Korshunov, Andrey [VerfasserIn] |
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| | Pfister, Stefan [VerfasserIn] |
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| | Rutkowski, Stefan [VerfasserIn] |
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| | Milde, Till [VerfasserIn] |
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| Titel: | Identification of low and very high-risk patients with non-WNT/non-SHH medulloblastoma by improved clinico-molecular stratification of the HIT2000 and I-HIT-MED cohorts |
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| Verf.angabe: | Martin Mynarek, Denise Obrecht, Martin Sill, Dominik Sturm, Katja Kloth-Stachnau, Florian Selt, Jonas Ecker, Katja von Hoff, Björn-Ole Juhnke, Tobias Goschzik, Torsten Pietsch, Michael Bockmayr, Marcel Kool, Andreas von Deimling, Olaf Witt, Ulrich Schüller, Martin Benesch, Nicolas U. Gerber, Felix Sahm, David T. W. Jones, Andrey Korshunov, Stefan M. Pfister, Stefan Rutkowski, Till Milde |
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| E-Jahr: | 2023 |
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| Jahr: | 2 December 2022 |
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| Umfang: | 16 S. |
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| Illustrationen: | Illustrationen, Diagramme |
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| Fussnoten: | Gesehen am 20.12.2023 |
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| Titel Quelle: | Enthalten in: Acta neuropathologica |
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| Ort Quelle: | Berlin : Springer, 1961 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 145(2023), 1, Seite 97-112 |
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| ISSN Quelle: | 1432-0533 |
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| Abstract: | Molecular groups of medulloblastoma (MB) are well established. Novel risk stratification parameters include Group 3/4 (non-WNT/non-SHH) methylation subgroups I-VIII or whole-chromosomal aberration (WCA) phenotypes. This study investigates the integration of clinical and molecular parameters to improve risk stratification of non-WNT/non-SHH MB. Non-WNT/non-SHH MB from the HIT2000 study and the HIT-MED registries were selected based on availability of DNA-methylation profiling data. MYC or MYCN amplification and WCA of chromosomes 7, 8, and 11 were inferred from methylation array-based copy number profiles. In total, 403 non-WNT/non-SHH MB were identified, 346/403 (86%) had a methylation class family Group 3/4 methylation score (classifier v11b6) ≥ 0.9, and 294/346 (73%) were included in the risk stratification modeling based on Group 3 or 4 score (v11b6) ≥ 0.8 and subgroup I-VIII score (mb_g34) ≥ 0.8. Group 3 MB (5y-PFS, survival estimation ± standard deviation: 41.4 ± 4.6%; 5y-OS: 48.8 ± 5.0%) showed poorer survival compared to Group 4 (5y-PFS: 68.2 ± 3.7%; 5y-OS: 84.8 ± 2.8%). Subgroups II (5y-PFS: 27.6 ± 8.2%) and III (5y-PFS: 37.5 ± 7.9%) showed the poorest and subgroup VI (5y-PFS: 76.6 ± 7.9%), VII (5y-PFS: 75.9 ± 7.2%), and VIII (5y-PFS: 66.6 ± 5.8%) the best survival. Multivariate analysis revealed subgroup in combination with WCA phenotype to best predict risk of progression and death. The integration of clinical (age, M and R status) and molecular (MYC/N, subgroup, WCA phenotype) variables identified a low-risk stratum with a 5y-PFS of 94 ± 5.7 and a very high-risk stratum with a 5y-PFS of 29 ± 6.1%. Validation in an international MB cohort confirmed the combined stratification scheme with 82.1 ± 6.0% 5y-PFS in the low and 47.5 ± 4.1% in very high-risk groups, and outperformed the clinical model. These newly identified clinico-molecular low-risk and very high-risk strata, accounting for 6%, and 21% of non-WNT/non-SHH MB patients, respectively, may improve future treatment stratification. |
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| DOI: | doi:10.1007/s00401-022-02522-4 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1007/s00401-022-02522-4 |
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| | DOI: https://doi.org/10.1007/s00401-022-02522-4 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Group 3/4 |
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| | Medulloblastoma |
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| | Non-WNT/non-SHH |
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| | Risk stratification |
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| K10plus-PPN: | 1876596775 |
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| Verknüpfungen: | → Zeitschrift |
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Identification of low and very high-risk patients with non-WNT/non-SHH medulloblastoma by improved clinico-molecular stratification of the HIT2000 and I-HIT-MED cohorts / Mynarek, Martin [VerfasserIn]; 2 December 2022 (Online-Ressource)
