Molecular stratification of medulloblastoma

• Verfasst von: Goschzik, Tobias [VerfasserIn]
• Verfasst von: Pfister, Stefan [VerfasserIn]
• Titel: Molecular stratification of medulloblastoma
• Titelzusatz: comparison of histological and genetic methods to detect Wnt activated tumours
• Verf.angabe: Tobias Goschzik, Anja Zur Mühlen, Glen Kristiansen, Christine Haberler, Harald Stefanits, Carsten Friedrich, Katja von Hoff, Stefan Rutkowski, Stefan M. Pfister and Torsten Pietsch
• Umfang: 10 S.
• Fussnoten: Gesehen am 13.06.2017
• Titel Quelle: Enthalten in: Neuropathology & applied neurobiology
• Jahr Quelle: 2015
• Band/Heft Quelle: 41(2015), 2, S. 135-144
• ISSN Quelle: 1365-2990
• DOI: doi:10.1111/nan.12161
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1559719745

Abstract

AIMS: Wnt activation in medulloblastomas is associated with good outcome. Upfront testing and risk-adapted stratification of patients will be done in future clinical studies. In a cohort of 186 paediatric medulloblastomas our aim was to identify the optimal methods in standard clinical practice to detect this subgroup. METHODS: Nuclear accumulation of β-catenin was analysed by immunohistochemistry (IHC). DNA of FFPE tissue was amplified by PCR for single-strand conformation polymorphism analysis and direct sequencing of CTNNB1 exon 3. Copy number of chromosome 6 was analysed by multiplex ligation-dependent probe amplification and molecular inversion profiling.RESULTS: Different automated immunostaining systems showed similar results. Twenty-one of 186 samples had nuclear accumulation in ≥5% of cells, 17 samples showed <5% β-catenin positive nuclei. None of these 17 cases had CTNNB1 mutations, but 18 of 21 cases with ≥5% accumulation did, identifying these 18 cases as Wnt-subgroup medulloblastomas. Fifteen of 18 mutated cases showed monosomy 6, 3 had balanced chromosome 6. On the contrary, none of the CTNNB1 wild-type tumours had monosomy 6. CONCLUSIONS: Standard neuropathological evaluation of medulloblastoma samples should include IHC of β-catenin because tumours with high nuclear accumulation of β-catenin most probably belong to the Wnt subgroup of medulloblastomas. Still, IHC alone may be insufficient to detect all Wnt cases. Similarly, chromosome 6 aberrations were not present in all CTNNB1-mutated cases. Therefore, we conclude that sequencing analysis of CTNNB1 exon 3 in combination with β-catenin IHC (possibly as pre-screening method) is a feasible and cost-efficient way for the determination of Wnt medulloblastomas.