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A microdeletion event at 19q13.43 in IDH-mutant astrocytomas is strongly correlated with MYC overexpression

MYC dysregulation is pivotal in the onset and progression of IDH-mutant gliomas, mostly driven by copy-number alterations, regulatory element alterations, or epigenetic changes. Our pilot analysis uncovered instances of relative MYC overexpression without alterations in the proximal MYC network (PMN...

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Hauptverfasser: Ülgen, Ege (VerfasserIn) , Gerlevik, Umut (VerfasserIn) , Gerlevik, Sıla (VerfasserIn) , Oktay, Yavuz (VerfasserIn) , Sezerman, Osman Uğur (VerfasserIn) , Turcan, S̨evin (VerfasserIn) , Ozduman, Koray (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 14 June 2024
In: Acta Neuropathologica Communications
Year: 2024, Jahrgang: 12, Pages: 1-11
ISSN:2051-5960
DOI:10.1186/s40478-024-01811-1
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1186/s40478-024-01811-1
Volltext
Verfasserangaben:Ege Ülgen, Umut Gerlevik, Sıla Gerlevik, Yavuz Oktay, Osman Uğur Sezerman, Şevin Turcan and Koray Ozduman
Beschreibung
Zusammenfassung:MYC dysregulation is pivotal in the onset and progression of IDH-mutant gliomas, mostly driven by copy-number alterations, regulatory element alterations, or epigenetic changes. Our pilot analysis uncovered instances of relative MYC overexpression without alterations in the proximal MYC network (PMN), prompting a deeper investigation into potential novel oncogenic mechanisms. Analysing comprehensive genomics profiles of 236 “IDH-mutant 1p/19q non-co-deleted” lower-grade gliomas from The Cancer Genome Atlas, we identified somatic genomic alterations within the PMN. In tumours without PMN-alterations but with MYC-overexpression, genes correlated with MYC-overexpression were identified. Our analyses yielded that 86/236 of astrocytomas exhibited no PMN-alterations, a subset of 21/86 displaying relative MYC overexpression. Within this subset, we discovered 42 genes inversely correlated with relative MYC expression, all on 19q. Further analysis pinpointed a minimal common region at 19q13.43, encompassing 15 genes. The inverse correlations of these 15 genes with relative MYC overexpression were re-confirmed using independent scRNAseq data. Further, the micro-deleted astrocytoma subset displayed significantly higher genomic instability compared to WT cases, but lower instability compared to PMN-hit cases. This newly identified 19q micro-deletion represents a potential novel mechanism underlying MYC dysregulation in astrocytomas. Given the prominence of 19q loss in IDH-mutant gliomas, our findings bear significant implications for understanding gliomagenesis.
Beschreibung:Gesehen am 27.11.2024
Beschreibung:Online Resource
ISSN:2051-5960
DOI:10.1186/s40478-024-01811-1

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