Dixon, JR;
Xu, J;
Dileep, V;
Zhan, Y;
Songs, F;
Le, VT;
Yardimci, GA;
... Yue, F; + view all
(2018)
Integrative detection and analysis of structural variation in cancer genomes.
Nature Genetics
, 50
pp. 1388-1398.
10.1038/s41588-018-0195-8.
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Abstract
Structural variants (SVs) can contribute to oncogenesis through a variety of mechanisms. Despite their importance, the identification of SVs in cancer genomes remains challenging. Here, we present a framework that integrates optical mapping, high-throughput chromosome conformation capture (Hi-C), and whole-genome sequencing to systematically detect SVs in a variety of normal or cancer samples and cell lines. We identify the unique strengths of each method and demonstrate that only integrative approaches can comprehensively identify SVs in the genome. By combining Hi-C and optical mapping, we resolve complex SVs and phase multiple SV events to a single haplotype. Furthermore, we observe widespread structural variation events affecting the functions of noncoding sequences, including the deletion of distal regulatory sequences, alteration of DNA replication timing, and the creation of novel three-dimensional chromatin structural domains. Our results indicate that noncoding SVs may be underappreciated mutational drivers in cancer genomes.
| Type: | Article |
|---|---|
| Title: | Integrative detection and analysis of structural variation in cancer genomes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41588-018-0195-8 |
| Publisher version: | https://doi.org/10.1038/s41588-018-0195-8 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, CELL-LINES, SEQ, EXPRESSION, GENE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10060921 |
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