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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Mynarek, M; Obrecht, D; Sill, M; Sturm, D; Kloth-Stachnau, K; Selt, F; Ecker, J; von Hoff, K; Juhnke, BO; Goschzik, T; Pietsch, T; Bockmayr, M; Kool, M; von Deimling, A; Witt, O; Schuller, U; Benesch, M; Gerber, NU; Sahm, F; Jones, DTW; Korshunov, A; Pfister, SM; Rutkowski, S; Milde, T.
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
ACTA NEUROPATHOL. 2023; 145(1): 97-112. Doi: 10.1007/s00401-022-02522-4 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Benesch Martin

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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.

Find related publications in this database (Keywords)
Group 3
Risk stratification
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