Universität zu Köln

Burkert, Martin ORCID: 0000-0002-6721-9985, Blanc, Eric, Thiessen, Nina, Weber, Christiane, Toedling, Joern, Monti, Remo, Dombrowe, Victoria M., Stella de Biase, Maria, Kaufmann, Tom L., Haase, Kerstin, Waszak, Sebastian M., Eggert, Angelika, Beule, Dieter, Schulte, Johannes H., Ohler, Uwe and Schwarz, Roland F. ORCID: 0000-0001-9155-4268 (2024). Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma. iScience, 27 (10). pp. 1-22. Elsevier. ISSN 2589-0042

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Abstract

[Artikel-Nr.: 110918] Telomere maintenance in neuroblastoma is linked to poor outcome and caused by either telomerase reverse transcriptase (TERT) activation or through alternative lengthening of telomeres (ALT). In contrast to TERT activation, commonly caused by genomic rearrangements or MYCN amplification, ALT is less well understood. Alterations at the ATRX locus are key drivers of ALT but only present in ∼50% of ALT tumors. To identify potential new pathways to telomere maintenance, we investigate allele-specific gene dosage effects from whole genomes and transcriptomes in 115 primary neuroblastomas. We show that copy-number dosage deregulates telomere maintenance, genomic stability, and neuronal pathways and identify up- regulation of variants of histone H3 and H2A as a potential alternative pathway to ALT. We investigate the interplay between TERT activation, overexpression and copy-number dosage and reveal loss of imprinting at the RTL1 gene associated with poor clinical outcome. These results highlight the importance of gene dosage in key oncogenic mechanisms in neuroblastoma.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Burkert, Martin UNSPECIFIED https://orcid.org/0000-0002-6721-9985 UNSPECIFIED Blanc, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiessen, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Toedling, Joern UNSPECIFIED UNSPECIFIED UNSPECIFIED Monti, Remo UNSPECIFIED UNSPECIFIED UNSPECIFIED Dombrowe, Victoria M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stella de Biase, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaufmann, Tom L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Haase, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Waszak, Sebastian M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eggert, Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED Beule, Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulte, Johannes H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ohler, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Roland F. UNSPECIFIED https://orcid.org/0000-0001-9155-4268 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-814426
Identification Number:	10.1016/j.isci.2024.110918
Journal or Publication Title:	iScience
Volume:	27
Number:	10
Page Range:	pp. 1-22
Number of Pages:	22
Date:	October 2024
Publisher:	Elsevier
ISSN:	2589-0042
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Weitere > Centrum für integrierte Onkologie (CIO)
Subjects:	Life sciences Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Genomics ; Molecular biology ; Cell biology ; Transcriptomics English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81442