RT Journal Article SR Electronic T1 An Integrative Framework for Detecting Structural Variations in Cancer Genomes JF bioRxiv FD Cold Spring Harbor Laboratory SP 119651 DO 10.1101/119651 A1 Jesse R. Dixon A1 Jie Xu A1 Vishnu Dileep A1 Ye Zhan A1 Fan Song A1 Victoria T. Le A1 Galip Gürkan Yardimci A1 Abhijit Chakraborty A1 Darrin V. Bann A1 Yanli Wang A1 Royden Clark A1 Lijun Zhang A1 Hongbo Yang A1 Tingting Liu A1 Sriranga Iyyanki A1 Lin An A1 Christopher Pool A1 Takayo Sasaki A1 Juan Carlos Rivera Mulia A1 Hakan Ozadam A1 Bryan R. Lajoie A1 Rajinder Kaul A1 Michael Buckley A1 Kristen Lee A1 Morgan Diegel A1 Dubravka Pezic A1 Christina Ernst A1 Suzana Hadjur A1 Duncan T. Odom A1 John A. Stamatoyannopoulos A1 James R. Broach A1 Ross Hardison A1 Ferhat Ay A1 William Stafford Noble A1 Job Dekker A1 David M. Gilbert A1 Feng Yue YR 2017 UL http://biorxiv.org/content/early/2017/03/28/119651.abstract AB Structural variants can contribute to oncogenesis through a variety of mechanisms, yet, despite their importance, the identification of structural variants in cancer genomes remains challenging. Here, we present an integrative framework for comprehensively identifying structural variation in cancer genomes. For the first time, we apply next-generation optical mapping, high-throughput chromosome conformation capture (Hi-C), and whole genome sequencing to systematically detect SVs in a variety of cancer cells.Using this approach, we identify and characterize structural variants in up to 29 commonly used normal and cancer cell lines. We find that each method has unique strengths in identifying different classes of structural variants and at different scales, suggesting that integrative approaches are likely the only way to comprehensively identify structural variants in the genome. Studying the impact of the structural variants in cancer cell lines, we identify widespread structural variation events affecting the functions of non-coding sequences in the genome, including the deletion of distal regulatory sequences, alteration of DNA replication timing, and the creation of novel 3D chromatin structural domains.These results underscore the importance of comprehensive structural variant identification and indicate that non-coding structural variation may be an underappreciated mutational process in cancer genomes.