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SHH medulloblastoma in a young adult with a TCF4 germline pathogenic variation

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Acknowledgements

We thank Joshua Waterfall for his help in writing the manuscript.

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Authors and Affiliations

  1. Unité de Génétique Somatique, Institut Curie, Paris, France

    Maud Blanluet, Julien Masliah-Planchon, Christine Bourneix, Gaëlle Pierron & Olivier Delattre

  2. Pediatric Oncology Department, SIREDO Oncology Centre (Care, Innovation, Research in Pediatric, Adolescent and Young Adults Oncology), Institut Curie, 26, rue d’Ulm, 75248, Paris Cedex 05, France

    Julien Masliah-Planchon, Mamy Andrianteranagna, Gaëlle Pierron, Olivier Delattre, François Doz & Franck Bourdeaut

  3. UF de Génétique Moléculaire, Hôpital Armand Trousseau, APHP, Paris, France

    Irina Giurgea

  4. Sorbonne Université, INSERM, UMR S933, Paris, France

    Irina Giurgea

  5. Departement de Neuropathologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France

    Franck Bielle

  6. INSERM U900, Institut Curie, Paris, France

    Elodie Girard

  7. Neurochirurgie, GH Pitie-Salpêtrière-Charles Foix, APHP, Paris, France

    Stéphane Clemenceau

  8. Centre de Référence Maladies Rares “Malformations et Maladies Congénitales du Cervelet”, et Département de Génétique, Hôpital Armand Trousseau, GHUEP, APHP, Paris, France

    Lydie Burglen

  9. Département de Neuropédiatrie, Hôpital Armand Trousseau, APHP, Paris, France

    Diane Doummar

  10. Translational Research Department, Genomics Platform, Institut Curie, PSL Research University, Paris, 75248, France

    Audrey Rapinat & David Gentien

  11. Sorbonne Université, Inserm, UMS Omique, Plateforme Post-Génomique de la Pitié-Salpêtrière, P3S, 75013, Paris, France

    Badreddine Mohand Oumoussa

  12. Université Paris Sud, Université Paris-Saclay, CNRS, UMR 3347, INSERM U1021, Orsay, France

    Olivier Ayrault & Celio Pouponnot

  13. Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France

    Olivier Ayrault & Celio Pouponnot

  14. Inserm U830, PSL Université, Institut Curie, Paris, France

    Olivier Delattre & Franck Bourdeaut

  15. Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    François Doz

Authors
  1. Maud Blanluet
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  2. Julien Masliah-Planchon
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  3. Irina Giurgea
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  8. Christine Bourneix
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  10. Diane Doummar
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  11. Audrey Rapinat
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  12. Badreddine Mohand Oumoussa
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  13. Olivier Ayrault
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  14. Celio Pouponnot
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  15. David Gentien
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  16. Gaëlle Pierron
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  17. Olivier Delattre
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  18. François Doz
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  19. Franck Bourdeaut
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Corresponding author

Correspondence to Franck Bourdeaut.

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401_2019_1983_MOESM1_ESM.pptx

Supplementary Figure 1. Histopathological features of the tumor. (a) Hematoxylin and eosin staining showed a histological aspect of classic medulloblastoma with necrosis. (b) Immunostaining showed a diffusely high Ki67 proliferation index, (c) a maintained expression of SMARCB1/INI1, and (d) a mild positivity of P53. (e) Reticulin staining showed no reticulinic network between tumor cells. (f) Immunostaining showed a membrane staining for Beta-catenin, and (g) a strong positivity for Filamin-1 and (h) GAB1 favoring the genetic group of SHH-activated medulloblastomas (PPTX 624 kb)

401_2019_1983_MOESM2_ESM.pptx

Supplementary Figure 2. Methylation and genomic tumor data. (a) t-distributed Stochastic Neighbor Embedding (t-SNE) analysis using DNA methylation data (generated using HumanMethylation450K array type) of glioblastoma (GBM) and medulloblastoma (MB) samples published in Capper et al. (2018) [2] and DNA methylation data of our case (generated using HumanMethylationEPIC array type) named MB699. (b) MNP2.0-based DNA methylation class prediction calibrated scores for our case (DKFZ classifier version: 11b4). The other scores (data not shown) are inferior to 0.01. (c) Analysis of tumor DNA of our case by the Curie Institute custom cancer panel assessing known cancer-related genes (8 alterations), compared with the proportion of relevant tumor DNA alterations of these genes for all SHH MB (SHH MB column) and TCF4 mutated SHH MB (TCF4 mutated SHH MB column), from Northcott et al. (2017) [6] (PPTX 122 kb)

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Blanluet, M., Masliah-Planchon, J., Giurgea, I. et al. SHH medulloblastoma in a young adult with a TCF4 germline pathogenic variation. Acta Neuropathol 137, 675–678 (2019). https://doi.org/10.1007/s00401-019-01983-4

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