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024 7 _ |a 10.1111/nan.12161
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024 7 _ |a 0305-1846
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024 7 _ |a 1365-2990
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037 _ _ |a DKFZ-2017-02637
041 _ _ |a eng
082 _ _ |a 610
100 1 _ |a Goschzik, Tobias
|b 0
245 _ _ |a Molecular stratification of medulloblastoma: comparison of histological and genetic methods to detect Wnt activated tumours.
260 _ _ |a Oxford [u.a.]
|c 2015
|b Wiley-Blackwell
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.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.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.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.
536 _ _ |a 312 - Functional and structural genomics (POF3-312)
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650 _ 7 |a CTNNB1 protein, human
|2 NLM Chemicals
650 _ 7 |a beta Catenin
|2 NLM Chemicals
700 1 _ |a Zur Mühlen, Anja
|b 1
700 1 _ |a Kristiansen, Glen
|b 2
700 1 _ |a Haberler, Christine
|b 3
700 1 _ |a Stefanits, Harald
|b 4
700 1 _ |a Friedrich, Carsten
|b 5
700 1 _ |a von Hoff, Katja
|b 6
700 1 _ |a Rutkowski, Stefan
|b 7
700 1 _ |a Pfister, Stefan
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700 1 _ |a Pietsch, Torsten
|b 9
773 _ _ |a 10.1111/nan.12161
|g Vol. 41, no. 2, p. 135 - 144
|0 PERI:(DE-600)2008293-9
|n 2
|p 135 - 144
|t Neuropathology & applied neurobiology
|v 41
|y 2015
|x 0305-1846
909 C O |o oai:inrepo02.dkfz.de:126609
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910 1 _ |a Deutsches Krebsforschungszentrum
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