Title

Integrative detection and analysis of structural variation in cancer genomes

UMMS Affiliation

Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology

Publication Date

2018-10

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cancer Biology | Cells | Computational Biology | Genetic Phenomena | Genomics | Integrative Biology | Molecular Biology | Structural Biology | Systems Biology

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.

Keywords

cancer genomes, structural variants

DOI of Published Version

10.1038/s41588-018-0195-8

Source

Nat Genet. 2018 Oct;50(10):1388-1398. doi: 10.1038/s41588-018-0195-8. Epub 2018 Sep 10. Link to article on publisher's site

Journal/Book/Conference Title

Nature genetics

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

30202056

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