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@ARTICLE{Pags:180677,
author = {M. Pagès and M.-A. Debily and F. Fina and D. T. W.
Jones$^*$ and R. Saffroy and D. Castel and T. Blauwblomme
and A. Métais and M. Bourgeois and E. Lechapt-Zalcman and
A. Tauziède-Espariat and F. Andreiuolo and F. Chrétien and
J. Grill and N. Boddaert and D. Figarella-Branger and R.
Beroukhim and P. Varlet},
title = {{T}he genomic landscape of dysembryoplastic neuroepithelial
tumours and a comprehensive analysis of recurrent cases.},
journal = {Neuropathology $\&$ applied neurobiology},
volume = {48},
number = {6},
issn = {0305-1846},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2022-01477},
pages = {e12834},
year = {2022},
note = {2022 Oct;48(6):e12834},
abstract = {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.},
keywords = {DNA methylation profiling (Other) / Dysembryoplastic
neuroepithelial tumours (Other) / FGFR1 (Other) /
Glioneuronal tumours (Other) / Integrated diagnosis (Other)
/ Isomorphic glioma (Other) / Molecular pathology (Other) /
PLNTY (Other) / Paediatric low-grade gliomas (Other)},
cin = {B360},
ddc = {610},
cid = {I:(DE-He78)B360-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35836307},
doi = {10.1111/nan.12834},
url = {https://inrepo02.dkfz.de/record/180677},
}