Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 02 2021
24 02 2021
Historique:
received:
19
05
2020
accepted:
13
01
2021
entrez:
25
2
2021
pubmed:
26
2
2021
medline:
4
3
2021
Statut:
epublish
Résumé
Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas (n = 760) and characterize its features using multi-omics profiling. ALT-positive tumors are molecularly distinct from other neuroblastoma subtypes and enriched in a population-based clinical sequencing study cohort for relapsed cases. They display reduced ATRX/DAXX complex abundance, due to either ATRX mutations (55%) or low protein expression. The heterochromatic histone mark H3K9me3 recognized by ATRX is enriched at the telomeres of ALT-positive tumors. Notably, we find a high frequency of telomeric repeat loci with a neuroblastoma ALT-specific hotspot on chr1q42.2 and loss of the adjacent chromosomal segment forming a neo-telomere. ALT-positive neuroblastomas proliferate slowly, which is reflected by a protracted clinical course of disease. Nevertheless, children with an ALT-positive neuroblastoma have dismal outcome.
Identifiants
pubmed: 33627664
doi: 10.1038/s41467-021-21247-8
pii: 10.1038/s41467-021-21247-8
pmc: PMC7904810
doi:
Substances chimiques
Proteome
0
X-linked Nuclear Protein
EC 3.6.4.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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