The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases

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.

Automated summary

Dysembryoplastic neuroepithelial tumour (DNT) is a challenging glioneuronal tumour with diverse histological features. The study used comprehensive analysis techniques to characterize 82 DNTs, revealing differences between specific and non-specific/diffuse DNTs, as well as identifying additional genomic alterations in a subset of DNTs.