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DOI: 10.1055/s-0033-1343649
Molecular stratification of medulloblastoma: Comparison of histological and genetical methods to detect Wnt activated tumors
In a cohort of 188 pediatric medulloblastomas our aim was to identify the optimal methods in standard clinical practice to detect those with Wnt activation, which is associated with good outcome. Therefore, nuclear accumulation of ß-Catenin was analyzed by immunohistochemistry (IHC) using 3 different automated staining systems. Also SSCP (single-strand conformation polymorphism) analysis and direct Sanger sequencing of CTNNB1 exon 3 was done. Finally, copy number aberrations of chromosome 6 were analyzed by MLPA (multiplex ligation-dependent probe amplification) and by molecular inversion profiling. 22 samples showed nuclear accumulation in > 5% of tumor cells but only 18 of them had CTNNB1 mutations. SSCP analysis only showed DNA bands with aberrant migration in 3 of the 18 mutated samples representing 2 different mutations. Monosomy 6 was present in most but not all mutated cases. Therefore, we conclude that sequencing analysis of CTNNB1 exon 3 in combination with ß-Catenin IHC (possibly as pre-screening method) is a feasible, fast and cost-efficient approach for the determination of Wnt subgroup medulloblastomas.