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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},
}