PT - JOURNAL ARTICLE AU - Jesse R. Dixon AU - Jie Xu AU - Vishnu Dileep AU - Ye Zhan AU - Fan Song AU - Victoria T. Le AU - Galip Gürkan Yardimci AU - Abhijit Chakraborty AU - Darrin V. Bann AU - Yanli Wang AU - Royden Clark AU - Lijun Zhang AU - Hongbo Yang AU - Tingting Liu AU - Sriranga Iyyanki AU - Lin An AU - Christopher Pool AU - Takayo Sasaki AU - Juan Carlos Rivera Mulia AU - Hakan Ozadam AU - Bryan R. Lajoie AU - Rajinder Kaul AU - Michael Buckley AU - Kristen Lee AU - Morgan Diegel AU - Dubravka Pezic AU - Christina Ernst AU - Suzana Hadjur AU - Duncan T. Odom AU - John A. Stamatoyannopoulos AU - James R. Broach AU - Ross Hardison AU - Ferhat Ay AU - William Stafford Noble AU - Job Dekker AU - David M. Gilbert AU - Feng Yue TI - An Integrative Framework for Detecting Structural Variations in Cancer Genomes AID - 10.1101/119651 DP - 2017 Jan 01 TA - bioRxiv PG - 119651 4099 - http://biorxiv.org/content/early/2017/03/28/119651.short 4100 - http://biorxiv.org/content/early/2017/03/28/119651.full 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.