Linked-read based analysis of the medulloblastoma genome.
RNA sequencing
enhancer hijacking
extrachromosomal DNA
linked-reads
medulloblastoma
whole-genome sequencing
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2023
2023
Historique:
received:
12
05
2023
accepted:
06
07
2023
medline:
14
8
2023
pubmed:
14
8
2023
entrez:
14
8
2023
Statut:
epublish
Résumé
Medulloblastoma is the most common type of malignant pediatric brain tumor with group 4 medulloblastomas (G4 MBs) accounting for 40% of cases. However, the molecular mechanisms that underlie this subgroup are still poorly understood. Point mutations are detected in a large number of genes at low incidence per gene while the detection of complex structural variants in recurrently affected genes typically requires the application of long-read technologies. Here, we applied linked-read sequencing, which combines the long-range genome information of long-read sequencing with the high base pair accuracy of short read sequencing and very low sample input requirements. We demonstrate the detection of complex structural variants and point mutations in these tumors, and, for the first time, the detection of extrachromosomal DNA (ecDNA) with linked-reads. We provide further evidence for the high heterogeneity of somatic mutations in G4 MBs and add new complex events associated with it. We detected several enhancer-hijacking events, an ecDNA containing the
Identifiants
pubmed: 37576901
doi: 10.3389/fonc.2023.1221611
pmc: PMC10419201
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1221611Subventions
Organisme : NCI NIH HHS
ID : R01 CA159859
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA255369
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS106155
Pays : United States
Informations de copyright
Copyright © 2023 Zwaig, Johnston, Lee, Farooq, Gallo, Jabado, Taylor and Ragoussis.
Déclaration de conflit d'intérêts
Author HF was employed by the company BioBox Analytics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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