Discovery of Osteosarcoma Genomic Structural Variations with NanoChannel Array technology (Irys System)

Authors

• Y Jiang
• S Bilke
• S Oeser
• A Canela
• RW Walker
• J Lueders
• PS Meltzer

Abstract

Osteosarcoma (OS) is a primary malignant bone tumor with high morbidity that principally emerges in children and adolescents. Presently, the prognosis of OS patients remains poor due to resistance to chemotherapy, highlighting the need for new therapeutic approaches. As improvements in survival outcomes have largely plateaued, better understanding the whole-cancer genome mutation catalogues may provide new treatment approaches. However, understanding of the biological processes generating these mutations is limited. To address those challenges, we are utilizing Irys® genome mapping technology to comprehensively discover genome-wide Structural variants (SVs) and characterize complex regions of the OS genome using long single molecules (>150 kb) in a global fashion. Irys® System is a rapid genome-wide analysis method that confines and linearizes individual molecules of DNA to nearly 85% of their respective contour length. Once confined, extremely long DNA molecules (100 to 1,000 kilobases) are imaged with a custom three-color epifluorescence microscope. Genomic DNA is stained with YOYO and can be labeled specifically at the ‘GCTCTTC’ or ‘CCTCAGC’ sequence with different colored fluorescent probes allowing for each molecule to have a unique pattern and mapped to its corresponding location in a reference. By imaging hundreds of gigabases per run, a high-resolution genome map was assembled de novo from the extremely long single molecules, which retain the original context and architecture of the genome. This allows for the cataloging of complex repetitive regions and large-scale rearrangements. The advantages of genome mapping for rearrangement analysis can identify hallmark fusions as well as rearrangements from Osteosarcoma cancer cells.

Scientific Focus Area: Cancer Biology

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