%0 Journal Article
%A Pagès, Mélanie
%A Debily, Marie-Anne
%A Fina, Frédéric
%A Jones, David T W
%A Saffroy, Raphael
%A Castel, David
%A Blauwblomme, Thomas
%A Métais, Alice
%A Bourgeois, Marie
%A Lechapt-Zalcman, Emmanuèle
%A Tauziède-Espariat, Arnault
%A Andreiuolo, Felipe
%A Chrétien, Fabrice
%A Grill, Jacques
%A Boddaert, Nathalie
%A Figarella-Branger, Dominique
%A Beroukhim, Rameen
%A Varlet, Pascale
%T The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases.
%J Neuropathology & applied neurobiology
%V 48
%N 6
%@ 0305-1846
%C Oxford [u.a.]
%I Wiley-Blackwell
%M DKFZ-2022-01477
%P e12834
%D 2022
%Z 2022 Oct;48(6):e12834
%X 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.We used targeted methods (IHC, FISH, targeted sequencing) and large-scale genomic methodologies including DNA methylation profiling to perform an integrative analysis to better characterize a large retrospective cohort of 82 DNTs, enriched for tumours that showed progression on imaging.We confirmed that specific DNTs are characterized 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.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, a good prognosis but showing progression in some cases. The 'non-specific/diffuse DNTs' subgroup encompasses various recently described histo-molecular entities, such as PLNTY and diffuse astrocytoma, MYB or MYBL1-altered.
%K DNA methylation profiling (Other)
%K Dysembryoplastic neuroepithelial tumours (Other)
%K FGFR1 (Other)
%K Glioneuronal tumours (Other)
%K Integrated diagnosis (Other)
%K Isomorphic glioma (Other)
%K Molecular pathology (Other)
%K PLNTY (Other)
%K Paediatric low-grade gliomas (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35836307
%R 10.1111/nan.12834
%U https://inrepo02.dkfz.de/record/180677