Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures

Study ID Alternative Stable ID Type
EGAS00001006576 Other

Study Description

Cancer genomes harbor a broad spectrum of structural variants (SV) driving tumorigenesis, a relevant subset of which are likely to escape discovery in short reads. We employed Oxford Nanopore Technologies (ONT) sequencing in a paired diagnostic and post-therapy medulloblastoma to unravel the haplotype-resolved somatic genetic and epigenetic landscape. We assemble complex rearrangements and such associated with telomeric sequences, including a 1.55 Megabasepair chromothripsis event. We uncover a complex SV pattern termed "templated insertion thread", characterized by short (mostly less than 1kb) insertions showing prevalent self-concatenation into highly amplified structures of up to 50kbp in size. Templated insertion threads occur in 3% of cancers, with a prevalence ranging to 74% in liposarcoma, and frequent colocalization with chromothripsis. We also perform long-read based methylome profiling and discover allele-specific methylation (ASM) effects, complex rearrangements exhibiting differential methylation, and differential promoter methylation in seven cancer-driver genes. Our ... (Show More)

Study Datasets 6 datasets.

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Dataset ID Description Technology Samples
ONT (PromethION) sequencing of chromothriptic medulloblastoma. Three samples: blood, primary tumor, and relapse tumor. Includes a fourth low-coverage run that multiplexes blood and primary tumor.
PromethION 3
Illumina whole genome sequencing of Medulloblastoma Blood, Primary tumor, and Relapse tumor
HiSeq X Ten 1
Illumina RNA-sequencing of Medulloblastoma primary and relapse tumor.
Illumina HiSeq 2000 1
Circle-Seq experiment.
HiSeq X Ten 1
GridION 1
450k methylation arrays of primary and relapse tumor of a single case of sonic hedgehog medulloblastoma with Li-Fraumeni syndrome
HumanMethylation450 2

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