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@ARTICLE{Delaidelli:177225,
author = {A. Delaidelli and C. Dunham and M. Santi and G. L. Negri
and J. Triscott and O. Zheludkova and A. Golanov and M.
Ryzhova and K. Okonechnikov$^*$ and D. Schrimpf$^*$ and D.
Stichel$^*$ and D. W. Ellison and A. von Deimling$^*$ and M.
Kool$^*$ and S. Pfister$^*$ and V. Ramaswamy and A.
Korshunov$^*$ and M. D. Taylor and P. H. Sorensen},
title = {{C}linically {T}ractable {O}utcome {P}rediction of
non-{WNT}/non-{SHH} {M}edulloblastoma {B}ased on {TPD}52
{I}mmunohistochemistry in a {M}ulticohort {S}tudy.},
journal = {Clinical cancer research},
volume = {28},
number = {1},
issn = {1557-3265},
address = {Philadelphia, Pa. [u.a.]},
publisher = {AACR},
reportid = {DKFZ-2021-02359},
pages = {116-128},
year = {2022},
note = {2022 Jan 1;28(1):116-128},
abstract = {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.},
cin = {B062 / HD01 / B300},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B300-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34702771},
doi = {10.1158/1078-0432.CCR-21-2057},
url = {https://inrepo02.dkfz.de/record/177225},
}