von Bueren, André O.

[["dc.bibliographiccitation.firstpage","137"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","149"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Pietsch, Torsten"],["dc.contributor.author","Schmidt, Rene"],["dc.contributor.author","Remke, Marc"],["dc.contributor.author","Korshunov, Andrey"],["dc.contributor.author","Hovestadt, Volker"],["dc.contributor.author","Jones, David T. W."],["dc.contributor.author","Felsberg, Joerg"],["dc.contributor.author","Kaulich, Kerstin"],["dc.contributor.author","Goschzik, Tobias"],["dc.contributor.author","Kool, Marcel"],["dc.contributor.author","Northcott, Paul A."],["dc.contributor.author","von Hoff, Katja"],["dc.contributor.author","von Bueren, Andre Oscar"],["dc.contributor.author","Friedrich, Carsten"],["dc.contributor.author","Mynarek, Martin"],["dc.contributor.author","Skladny, Heyko"],["dc.contributor.author","Fleischhack, Gudrun"],["dc.contributor.author","Taylor, Michael D."],["dc.contributor.author","Cremer, Friedrich"],["dc.contributor.author","Lichter, Peter"],["dc.contributor.author","Faldum, Andreas"],["dc.contributor.author","Reifenberger, Guido"],["dc.contributor.author","Rutkowski, Stefan"],["dc.contributor.author","Pfister, Stefan M."],["dc.date.accessioned","2018-11-07T09:38:16Z"],["dc.date.available","2018-11-07T09:38:16Z"],["dc.date.issued","2014"],["dc.description.abstract","This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a test (n = 57) dataset in order to build and test a risk score for this population. Independent validation was performed in a non-overlapping cohort (n = 83). All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining \"intermediate molecular risk\" population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified, with speckled synaptophysin expression indicating worse outcome. Test and independent validation of the score confirmed significant discrimination of patients by risk profile. Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk stratification of medulloblastoma. A simple clinico-pathological risk score was identified, which was confirmed in a test set and by independent clinical validation."],["dc.identifier.doi","10.1007/s00401-014-1276-0"],["dc.identifier.isi","000338195600011"],["dc.identifier.pmid","24791927"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10264"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33033"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","174"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Zhukova, Nataliya"],["dc.contributor.author","Ramaswamy, Vijay"],["dc.contributor.author","Remke, Marc"],["dc.contributor.author","Martin, Dianna C."],["dc.contributor.author","Castelo-Branco, Pedro"],["dc.contributor.author","Zhang, Cindy H."],["dc.contributor.author","Fraser, Michael"],["dc.contributor.author","Tse, Ken"],["dc.contributor.author","Poon, Raymond"],["dc.contributor.author","Shih, David JH"],["dc.contributor.author","Baskin, Berivan"],["dc.contributor.author","Ray, Peter N."],["dc.contributor.author","Bouffet, Eric"],["dc.contributor.author","Dirks, Peter"],["dc.contributor.author","von Bueren, Andre O."],["dc.contributor.author","Pfaff, Elke"],["dc.contributor.author","Korshunov, Andrey"],["dc.contributor.author","Jones, David T.W."],["dc.contributor.author","Northcott, Paul A."],["dc.contributor.author","Kool, Marcel"],["dc.contributor.author","Pugh, Trevor J."],["dc.contributor.author","Pomeroy, Scott L."],["dc.contributor.author","Cho, Yoon-Jae"],["dc.contributor.author","Pietsch, Torsten"],["dc.contributor.author","Gessi, Marco"],["dc.contributor.author","Rutkowski, Stefan"],["dc.contributor.author","Bognár, Laszlo"],["dc.contributor.author","Cho, Byung-Kyu"],["dc.contributor.author","Eberhart, Charles G."],["dc.contributor.author","Conter, Cecile F."],["dc.contributor.author","Fouladi, Maryam"],["dc.contributor.author","French, Pim J."],["dc.contributor.author","Grajkowska, Wieslawa A."],["dc.contributor.author","Gupta, Nalin"],["dc.contributor.author","Hauser, Peter"],["dc.contributor.author","Jabado, Nada"],["dc.contributor.author","Vasiljevic, Alexandre"],["dc.contributor.author","Jung, Shin"],["dc.contributor.author","Kim, Seung-Ki"],["dc.contributor.author","Klekner, Almos"],["dc.contributor.author","Kumabe, Toshihiro"],["dc.contributor.author","Lach, Boleslaw"],["dc.contributor.author","Leonard, Jeffrey R."],["dc.contributor.author","Liau, Linda M."],["dc.contributor.author","Massimi, Luca"],["dc.contributor.author","Pollack, Ian F."],["dc.contributor.author","Ra, Young S."],["dc.contributor.author","Rubin, Joshua B."],["dc.contributor.author","Van Meir, Erwin G."],["dc.contributor.author","Wang, Kyu-Chang"],["dc.contributor.author","Weiss, William A."],["dc.contributor.author","Zitterbart, Karel"],["dc.contributor.author","Bristow, Robert G."],["dc.contributor.author","Alman, Benjamin"],["dc.contributor.author","Hawkins, Cynthia E."],["dc.contributor.author","Malkin, David"],["dc.contributor.author","Clifford, Steven C."],["dc.contributor.author","Pfister, Stefan M."],["dc.contributor.author","Taylor, Michael D."],["dc.contributor.author","Tabori, Uri"],["dc.date.accessioned","2019-07-09T11:40:53Z"],["dc.date.available","2019-07-09T11:40:53Z"],["dc.date.issued","2014"],["dc.description.abstract","TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6% ± 8.7%, respectively (p < 0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% ± 2% vs. 57.4% ± 1.8% (p < 0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5% ± 1.5% in lithium treated cells vs. 56.6 ± 3% (p < 0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% ± 8% for lithium treated cells vs. 27% ± 3% for untreated controls (p = 0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas."],["dc.identifier.doi","10.1186/s40478-014-0174-y"],["dc.identifier.fs","610476"],["dc.identifier.pmid","25539912"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11459"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58290"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0178351"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Andreiuolo, Felipe"],["dc.contributor.author","Le Teuff, Gwenael"],["dc.contributor.author","Bayar, Mohamed Amine"],["dc.contributor.author","Kilday, John-Paul"],["dc.contributor.author","Pietsch, Torsten"],["dc.contributor.author","von Bueren, Andre Oscar"],["dc.contributor.author","Witt, Hendrik"],["dc.contributor.author","Korshunov, Andrey"],["dc.contributor.author","Modena, Piergiorgio"],["dc.contributor.author","Pfister, Stefan M."],["dc.contributor.author","Pages, Melanie"],["dc.contributor.author","Castel, David"],["dc.contributor.author","Giangaspero, Felice"],["dc.contributor.author","Chimelli, Leila"],["dc.contributor.author","Varlet, Pascale"],["dc.contributor.author","Rutkowski, Stefan"],["dc.contributor.author","Frappaz, Didier"],["dc.contributor.author","Massimino, Maura"],["dc.contributor.author","Grundy, Richard"],["dc.contributor.author","Grill, Jacques"],["dc.date.accessioned","2018-11-07T10:22:41Z"],["dc.date.available","2018-11-07T10:22:41Z"],["dc.date.issued","2017"],["dc.description.abstract","Purpose Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. Experimental design This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS) was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed. Results Among complete cases with 5-year median follow-up (n = 470; 131 deaths), TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR) = 2.19 95%CI = [1.29; 3.76] (p = 0.004), while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004) in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295) in supratentorial (interaction p value = 0.015). The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group. Conclusion Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma."],["dc.identifier.doi","10.1371/journal.pone.0178351"],["dc.identifier.isi","000403364600009"],["dc.identifier.pmid","28617804"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14555"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42317"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]