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• W2054080294 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCIntroduction: Wnt activation in medulloblastomas is associated with good outcome. Therefore, upfront testing and risk-adapted stratification of the patients will be done in future clinical studies. In a cohort of 188 pediatric medulloblastomas our aim was to identify the optimal methods in standard clinical practice to detect this subgroup.Experimental procedures: Nuclear accumulation of s-Catenin in tumor cells was analyzed by immunohistochemistry (IHC) of sections from formalin-fixed paraffin-embedded (FFPE) tumor samples with 3 different automated immunostaining systems and subsequent neuropathological evaluation. Genomic DNA of FFPE tumor tissue from each sample was amplified by PCR for SSCP (single-strand conformation polymorphism) analysis and direct Sanger sequencing of CTNNB1 exon 3. Copy number aberrations of chromosome 6 were analyzed by MLPA (multiplex ligation-dependent probe amplification) using the same genomic DNA and were confirmed in a subset of cases by molecular invasion profiling.Results: The different automated immunostaining systems showed similar results even though s-Catenin staining intensity varied. 22 of 188 samples showed nuclear accumulation in >5% of tumor cells and further 21 samples showed ≤5% s-Catenin positive nuclei. None of the latter 21 cases had mutations in exon 3 of the CTNNB1 gene, but 18 of the 22 cases with >5% nuclear accumulation did, clearly identifying these 18 cases as Wnt-subgroup medulloblastomas. SSCP analysis only showed DNA bands with aberrant migration in 3 of the 18 mutated samples representing 2 different mutations. With MLPA and molecular invasion profiling the 4 cases with >5% nuclear accumulation but without CTNNB1 mutation also lacked monosomy 6, which is another known marker for Wnt subgroup medulloblastomas. 15 of the 18 mutated cases showed monosomy 6, but 3 had a balanced chromosome 6, indicating that monosomy 6 is present in most but not all Wnt cases. On the other hand, none of the CTNNB1 wildtype tumors showed monosomy 6.Conclusion: Standard neuropathological evaluation of medulloblastoma samples should include IHC of s-Catenin because tumors with high nuclear accumulation of s-Catenin most probably belong to the Wnt subgroup of medulloblastomas associated with a good outcome. Still, IHC alone may be insufficient because of low quality of paraffin tissue, technical problems or differences in scoring s-Catenin positive nuclei. Similar, chromosome 6 aberrations in MLPA/molecular invasion profiling were shown not to be present in all CTNNB1 -mutated cases. Therefore, we conclude that sequencing analysis of CTNNB1 exon 3 in combination with s-Catenin IHC (possibly as pre-screening method) is a feasible, fast and cost-efficient way for the determination of Wnt subgroup medulloblastomas.Citation Format: Tobias Goschzik, Anja zur Muhlen, Glen Kristiansen, Torsten Pietsch. Molecular stratification of medulloblastoma: comparison of histological and genetical methods to detect Wnt activated tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-83. doi:10.1158/1538-7445.AM2013-LB-83" @default.
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• W2054080294 date "2013-04-15" @default.
• W2054080294 modified "2023-09-27" @default.
• W2054080294 title "Abstract LB-83: Molecular stratification of medulloblastoma: comparison of histological and genetical methods to detect Wnt activated tumors." @default.
• W2054080294 doi "https://doi.org/10.1158/1538-7445.am2013-lb-83" @default.
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