Molecular stratification of medulloblastoma: comparison of histological and genetic methods to detect Wnt activated tumours
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 d...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 January 2015
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| In: |
Neuropathology & applied neurobiology
Year: 2015, Volume: 41, Issue: 2, Pages: 135-144 |
| ISSN: | 1365-2990 |
| DOI: | 10.1111/nan.12161 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1111/nan.12161
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| Author Notes: | Tobias Goschzik, Anja Zur Mühlen, Glen Kristiansen, Christine Haberler, Harald Stefanits, Carsten Friedrich, Katja von Hoff, Stefan Rutkowski, Stefan M. Pfister and Torsten Pietsch |
| Summary: | 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. |
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| Item Description: | Gesehen am 13.06.2017 |
| Physical Description: | Online Resource |
| ISSN: | 1365-2990 |
| DOI: | 10.1111/nan.12161 |