Optical mapping reveals a higher level of genomic architecture of chained fusions in cancer

• DOI: 10.1101/gr.227975.117
• Publication Date: 2018-04-04T20:40:29Z
• Authors: Eva K.F. Chan; Daniel L. Cameron; Desiree C. Petersen; Ruth J. Lyons; Benedetta F. Baldi; Anthony T. Papenfuss; David M. Thomas; Vanessa M. Hayes
• Keywords: Breakpoint; Optical mapping; Structural Variation; Chromothripsis

Genomic rearrangements are common in cancer, with demonstrated links to disease progression and treatment response. These can be complex, resulting fusions of multiple chromosomal fragments generation derivative chromosomes. Although methods exist for detecting individual fusions, they generally unable reconstruct complex chained events. To overcome these limitations, we adopted a new optical mapping approach, allowing megabase-length genome maps reconstructed rearranged genomes visualized without loss integrity. Whole-genome (Bionano Genomics) well-studied highly liposarcoma cell line resulted 3338 assembled consensus maps, including 72 fusion maps. represent 112.3 Mb genomic regions, illuminating the architecture content, order, orientation, size. Spanning junction 147 translocations, found total 28 interspersed sequences that could not aligned reference genome. Traversing using short-read sequencing breakpoint calls, were able identify place 399 within gaps, thus illustrating complementary nature sequencing. We demonstrate provides powerful approach capturing higher level architecture, creating scaffold renewed interpretation data particular relevance human cancer.