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

Autor: Ülgen E; Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem University, Istanbul, Turkey.; Department of Neurosurgery, School of Medicine, Acibadem University, 34752, Istanbul, Turkey., Gerlevik U; Department of Biochemistry, University of Oxford, Oxford, UK.; Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, Germany., Gerlevik S; Faculty of Life Sciences and Medicine, Comprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK., Oktay Y; Izmir Biomedicine and Genome Center, Izmir, Turkey.; Department of Medical Biology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey., Sezerman OU; Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem University, Istanbul, Turkey., Turcan Ş; Neurology Clinic and National Center for Tumor Diseases, Heidelberg University Hospital and Heidelberg University, Heidelberg, Germany., Ozduman K; Department of Neurosurgery, School of Medicine, Acibadem University, 34752, Istanbul, Turkey. koray.ozduman@icloud.com.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2024 Jun 14; Vol. 12 (1), pp. 95. Date of Electronic Publication: 2024 Jun 14.
DOI: 10.1186/s40478-024-01811-1
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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