The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases
© 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:48 |
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| Enthalten in: |
Neuropathology and applied neurobiology - 48(2022), 6 vom: 14. Okt., Seite e12834 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pagès, Mélanie [VerfasserIn] |
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| Links: |
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| Themen: |
DNA methylation profiling |
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| Anmerkungen: |
Date Completed 08.09.2022 Date Revised 10.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/nan.12834 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM343566060 |
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| 100 | 1 | |a Pagès, Mélanie |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases |
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| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a DNA methylation profiling | |
| 650 | 4 | |a FGFR1 | |
| 650 | 4 | |a dysembryoplastic neuroepithelial tumours | |
| 650 | 4 | |a glioneuronal tumours | |
| 650 | 4 | |a molecular pathology | |
| 650 | 4 | |a paediatric low-grade gliomas | |
| 700 | 1 | |a Debily, Marie-Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Fina, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a Jones, David T W |e verfasserin |4 aut | |
| 700 | 1 | |a Saffroy, Raphael |e verfasserin |4 aut | |
| 700 | 1 | |a Castel, David |e verfasserin |4 aut | |
| 700 | 1 | |a Blauwblomme, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Métais, Alice |e verfasserin |4 aut | |
| 700 | 1 | |a Bourgeois, Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Lechapt-Zalcman, Emmanuèle |e verfasserin |4 aut | |
| 700 | 1 | |a Tauziède-Espariat, Arnault |e verfasserin |4 aut | |
| 700 | 1 | |a Andreiuolo, Felipe |e verfasserin |4 aut | |
| 700 | 1 | |a Chrétien, Fabrice |e verfasserin |4 aut | |
| 700 | 1 | |a Grill, Jacques |e verfasserin |4 aut | |
| 700 | 1 | |a Boddaert, Nathalie |e verfasserin |4 aut | |
| 700 | 1 | |a Figarella-Branger, Dominique |e verfasserin |4 aut | |
| 700 | 1 | |a Beroukhim, Rameen |e verfasserin |4 aut | |
| 700 | 1 | |a Varlet, Pascale |e verfasserin |4 aut | |
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