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Article Dans Une Revue Nature Cancer Année : 2022

Structural variants shape driver combinations and outcomes in pediatric high-grade glioma

Frank Dubois
Ofer Shapira
  • Fonction : Auteur
Noah Greenwald
Travis Zack
  • Fonction : Auteur
Jeremiah Wala
  • Fonction : Auteur
Jessica Tsai
Audrey Baguette
Djihad Hadjadj
  • Fonction : Auteur
Ashot Harutyunyan
Mirjam Blattner-Johnson
  • Fonction : Auteur
Jayne Vogelzang
  • Fonction : Auteur
Cecilia Sousa
  • Fonction : Auteur
Kyung Shin Kang
  • Fonction : Auteur
Claire Sinai
  • Fonction : Auteur
Dayle Wang
Prasidda Khadka
  • Fonction : Auteur
Kathleen Lewis
  • Fonction : Auteur
Hayley Malkin
  • Fonction : Auteur
Patricia Ho
Ryan O’rourke
  • Fonction : Auteur
Shu Zhang
  • Fonction : Auteur
Rose Gold
  • Fonction : Auteur
Davy Deng
  • Fonction : Auteur
Jonathan Serrano
  • Fonction : Auteur
Matija Snuderl
  • Fonction : Auteur
Chris Jones
  • Fonction : Auteur
Karen Wright
  • Fonction : Auteur
Susan Chi
  • Fonction : Auteur
Claudia Kleinman
Liliana Goumnerova
Nada Jabado
David Jones
Mark Kieran
  • Fonction : Auteur
Keith Ligon
Rameen Beroukhim
Pratiti Bandopadhayay

Résumé

Abstract Aims Dysembryoplastic neuroepithelial tumour (DNT) is a glioneuronal tumour that is challenging to diagnose, with a wide spectrum of histological features. Three histopathological patterns have been described: specific DNTs (both the simple form and the complex form) comprising the specific glioneuronal element, and also the non‐specific/diffuse form which lacks it, and has unclear phenotype–genotype correlations with numerous differential diagnoses. Methods We used targeted methods (immunohistochemistry, fluorescence in situ hybridisation and targeted sequencing) and large‐scale genomic methodologies including DNA methylation profiling to perform an integrative analysis to better characterise a large retrospective cohort of 82 DNTs, enriched for tumours that showed progression on imaging. Results We confirmed that specific DNTs are characterised by a single driver event with a high frequency of FGFR1 variants. However, a subset of DNA methylation‐confirmed DNTs harbour alternative genomic alterations to FGFR1 duplication/mutation. We also demonstrated that a subset of DNTs sharing the same FGFR1 alterations can show in situ progression. In contrast to the specific forms, “non‐specific/diffuse DNTs” corresponded to a heterogeneous molecular group encompassing diverse, newly‐described, molecularly distinct entities. Conclusions Specific DNT is a homogeneous group of tumours sharing characteristics of paediatric low‐grade gliomas: a quiet genome with a recurrent genomic alteration in the RAS‐MAPK signalling pathway, a distinct DNA methylation profile and a good prognosis but showing progression in some cases. The “non‐specific/diffuse DNTs” subgroup encompasses various recently described histomolecular entities, such as PLNTY and diffuse astrocytoma, MYB or MYBL1 altered.

Dates et versions

hal-04493146 , version 1 (06-03-2024)

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Citer

Frank Dubois, Ofer Shapira, Noah Greenwald, Travis Zack, Jeremiah Wala, et al.. Structural variants shape driver combinations and outcomes in pediatric high-grade glioma. Nature Cancer, 2022, 3 (8), pp.994-1011. ⟨10.1038/s43018-022-00403-z⟩. ⟨hal-04493146⟩
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