BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas - CRCL-Mort cellulaire et cancers pédiatriques
Pré-Publication, Document De Travail Année : 2023

BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas

Swann Meyer
  • Fonction : Auteur
Clément Berthelot
  • Fonction : Auteur
Maud Hamadou
  • Fonction : Auteur
Adrien Bertrand-Chapel
Andria Rakotomalala
  • Fonction : Auteur
Line Manceau
  • Fonction : Auteur
Julia Tomine
  • Fonction : Auteur
Nicolas Lespinasse
  • Fonction : Auteur
Paul Lewandowski
  • Fonction : Auteur
Martine Cordier-Bussat
  • Fonction : Auteur
Laura Broutier
Aurélie Dutour
Isabelle Rochet
  • Fonction : Auteur
Jean-Yves Blay
Cyril Degletagne
Valéry Attignon
  • Fonction : Auteur
Angel Montero-Carcaboso
  • Fonction : Auteur
Alexandre Vasiljevic
  • Fonction : Auteur
Pascale Gilardi-Hebenstreit
  • Fonction : Auteur
Samuel Meignan
  • Fonction : Auteur
Pierre Leblond
  • Fonction : Auteur
Vanessa Ribes
Erika Cosset
Marie Castets

Résumé

Pediatric diffuse midline gliomas (pDMG) are an aggressive type of childhood cancer with a fatal outcome. Their major epigenetic determinism has become clear, notably with the identification of K27M mutations in histone H3. However, the synergistic oncogenic mechanisms that induce and maintain tumor cell phenotype have yet to be deciphered. In 20 to 30% of cases, these tumors have an altered BMP signaling pathway with an oncogenic mutation on the BMP type I receptor ALK2, encoded by ACVR1. However, the potential impact of the BMP pathway in tumors non-mutated for ACVR1 is less clear. By integrating bulk, single-cell and spatial transcriptomic data, we show here that the BMP signaling pathway is activated at similar levels between ACVR1 wild type and mutant tumors and identify BMP2 and BMP7 as putative activators of the pathway in a specific subpopulation of cells. By using both pediatric isogenic glioma lines genetically modified to overexpress H3.3K27M and patients-derived DIPG cell lines, we demonstrate that BMP2/7 synergizes with H3.3K27M to induce a transcriptomic rewiring associated with a quiescent but invasive cell state. These data suggest a generic oncogenic role for the BMP pathway in gliomagenesis of pDMG and pave the way for specific targeting of downstream effectors mediating the BMP/K27M crosstalk.
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Dates et versions

hal-04295430 , version 1 (20-11-2023)

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Paul Huchedé, Swann Meyer, Clément Berthelot, Maud Hamadou, Adrien Bertrand-Chapel, et al.. BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas. 2023. ⟨hal-04295430⟩
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