TY  - JOUR
AU  - Pagès, Mélanie
AU  - Debily, Marie-Anne
AU  - Fina, Frédéric
AU  - Jones, David T W
AU  - Saffroy, Raphael
AU  - Castel, David
AU  - Blauwblomme, Thomas
AU  - Métais, Alice
AU  - Bourgeois, Marie
AU  - Lechapt-Zalcman, Emmanuèle
AU  - Tauziède-Espariat, Arnault
AU  - Andreiuolo, Felipe
AU  - Chrétien, Fabrice
AU  - Grill, Jacques
AU  - Boddaert, Nathalie
AU  - Figarella-Branger, Dominique
AU  - Beroukhim, Rameen
AU  - Varlet, Pascale
TI  - The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases.
JO  - Neuropathology & applied neurobiology
VL  - 48
IS  - 6
SN  - 0305-1846
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - DKFZ-2022-01477
SP  - e12834
PY  - 2022
N1  - 2022 Oct;48(6):e12834
AB  - 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.
KW  - DNA methylation profiling (Other)
KW  - Dysembryoplastic neuroepithelial tumours (Other)
KW  - FGFR1 (Other)
KW  - Glioneuronal tumours (Other)
KW  - Integrated diagnosis (Other)
KW  - Isomorphic glioma (Other)
KW  - Molecular pathology (Other)
KW  - PLNTY (Other)
KW  - Paediatric low-grade gliomas (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:35836307
DO  - DOI:10.1111/nan.12834
UR  - https://inrepo02.dkfz.de/record/180677
ER  -