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| Item Type: | Article |
|---|---|
| Title: | Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures |
| Creators Name: | Rausch, T., Snajder, R., Leger, A., Simovic, M., Giurgiu, M., Villacorta, L., Henssen, A.G., Fröhling, S., Stegle, O., Birney, E., Bonder, M.J., Ernst, A. and Korbel, J.O. |
| Abstract: | Cancer genomes harbor a broad spectrum of structural variants (SVs) driving tumorigenesis, a relevant subset of which escape discovery using short-read sequencing. We employed Oxford Nanopore Technologies (ONT) long-read sequencing in a paired diagnostic and post-therapy medulloblastoma to unravel the haplotype-resolved somatic genetic and epigenetic landscape. We assembled complex rearrangements, including a 1.55-Mbp chromothripsis event, and we uncover a complex SV pattern termed templated insertion (TI) thread, characterized by short (mostly <1 kb) insertions showing prevalent self-concatenation into highly amplified structures of up to 50 kbp in size. TI threads occur in 3% of cancers, with a prevalence up 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 cancer-driver genes. Our study shows the advantage of long-read sequencing in the discovery and characterization of complex somatic rearrangements. |
| Keywords: | Long Read Sequencing, Cancer Genomics, Templated Insertions, Complex Rearrangements, Epigenetic Signatures, Nanopore Methylation Calling, Chromothripsis |
| Source: | Cell Genomics |
| ISSN: | 2666-979X |
| Publisher: | Cell Press |
| Volume: | 3 |
| Number: | 4 |
| Page Range: | 100281 |
| Date: | 12 April 2023 |
| Official Publication: | https://doi.org/10.1016/j.xgen.2023.100281 |
| PubMed: | View item in PubMed |
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