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| Home > Publications database > Clinically Tractable Outcome Prediction of non-WNT/non-SHH Medulloblastoma Based on TPD52 Immunohistochemistry in a Multicohort Study. > print |
| 001 | 177225 | ||
| 005 | 20240229133733.0 | ||
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| 100 | 1 | _ | |a Delaidelli, Alberto |b 0 |
| 245 | _ | _ | |a Clinically Tractable Outcome Prediction of non-WNT/non-SHH Medulloblastoma Based on TPD52 Immunohistochemistry in a Multicohort Study. |
| 260 | _ | _ | |a Philadelphia, Pa. [u.a.] |c 2022 |b AACR |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1642495629_14352 |2 PUB:(DE-HGF) |
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| 500 | _ | _ | |a 2022 Jan 1;28(1):116-128 |
| 520 | _ | _ | |a International consensus and the 2021 WHO classification recognize eight molecular subgroups among non-WNT/non-SHH (Group 3/4) medulloblastoma, representing ~60% of tumors. However, very few clinical centers worldwide possess the technical capabilities to determine DNA-methylation profiles or other molecular parameters of high-risk for Group 3/4 tumors. As a result, biomarker-driven risk stratification and therapy assignment constitutes a major challenge in medulloblastoma research. Here, we identify an immunohistochemistry (IHC) marker as a clinically tractable method for improved medulloblastoma risk stratification.We bioinformatically analyzed published medulloblastoma transcriptomes and proteomes identifying as a potential biomarker TPD52, whose IHC prognostic value was validated across three Group 3/4 medulloblastoma clinical cohorts (n = 387) treated with conventional therapies.TPD52 IHC positivity represented a significant independent predictor of early relapse and death for Group 3/4 medulloblastoma (HRs between 3.67-26.7 [95% CIs between 1.00-706.23], p = 0.05, 0.017 and 0.0058). Cross-validated survival models incorporating TPD52 IHC with clinical features outperformed existing state-of-the-art risk stratification schemes, and reclassified ~50% of patients into more appropriate risk categories. Finally, TPD52 immunopositivity was a predictive indicator of poor response to chemotherapy (HR 12.66 [95% CI 3.53-45.40], p < 0.0001), suggesting important implication for therapeutic choices.The current study redefines the approach to risk stratification in Group 3/4 medulloblastoma in global practice. Since integration of TPD52 IHC in classification algorithms significantly improved outcome prediction, this test could be rapidly adopted for risk stratification on a global scale, independently of advanced but technically challenging molecular profiling techniques. |
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| 700 | 1 | _ | |a Dunham, Christopher |b 1 |
| 700 | 1 | _ | |a Santi, Mariarita |b 2 |
| 700 | 1 | _ | |a Negri, Gian Luca |0 0000-0001-7722-8888 |b 3 |
| 700 | 1 | _ | |a Triscott, Joanna |b 4 |
| 700 | 1 | _ | |a Zheludkova, Olga |b 5 |
| 700 | 1 | _ | |a Golanov, Andrey |b 6 |
| 700 | 1 | _ | |a Ryzhova, Marina |b 7 |
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| 700 | 1 | _ | |a Ellison, David W |0 0000-0003-1239-7757 |b 11 |
| 700 | 1 | _ | |a von Deimling, Andreas |0 P:(DE-He78)a8a10626a848d31e70cfd96a133cc144 |b 12 |u dkfz |
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| 700 | 1 | _ | |a Taylor, Michael D |b 17 |
| 700 | 1 | _ | |a Sorensen, Poul H |b 18 |
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