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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. and Snajder, R. and Leger, A. and Simovic, M. and Giurgiu, M. and Villacorta, L. and Henssen, A.G. and Fröhling, S. and Stegle, O. and Birney, E. and Bonder, M.J. and 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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