Linked-read based analysis of the medulloblastoma genome.

Frontiers in oncology
Authors
Keywords
Abstract

INTRODUCTION: 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.METHODS: 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.RESULTS: 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.DISCUSSION: We detected several enhancer-hijacking events, an ecDNA containing the gene, and rare structural rearrangements, such a chromothripsis in a G4 medulloblastoma, chromoplexy involving 8 different chromosomes, a gene rearrangement, and a duplication.

Year of Publication
2023
Journal
Frontiers in oncology
Volume
13
Pages
1221611
Date Published
12/2023
ISSN
2234-943X
DOI
10.3389/fonc.2023.1221611
PubMed ID
37576901
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