Accumulation of structural variations (SVs) across the genome is a known trigger factor for oncogenesis. Structural mutations have been clearly implicated in a number of cancers, most notably translocations that result in druggable fusions involving genes such as NTRK, MPRSS2, RET, FGFR3, ALK, and ESR1.  Identifying these structural genomic alterations - accurately and comprehensively - is crucial for improving research and ultimately therapies for cancer patients, yet one of primary challenges when solely relied on short read sequencing and standard cytogenetic methods (e.g. karyotyping, FISH and chromosomal microarrays).
 
Whole genome imaging, enabled by the Bionano Saphyr® System, is quickly becoming established as a key method for detection of intractable types of structural variations. The Saphyr System images ultra-long, linearized DNA molecules labeled at specific sequence motifs. Comparative analysis of the label patterns over long contiguous reads across the whole genome, reveals structural variants (>500 bp), at sensitivities as high as 99%, with false positive rates below 2%, even at allele fractions as low as 5%. Whole genome imaging can accurately assemble and assay relevant regions for complex genomic disorders like cancer as well as for repeat expansion disorders, even those involving very large segmental duplications. Bioinformatics tools, an integral part of the Saphyr System, effectively prioritize the ~6000 structural variants based on the estimated frequency in a control population, whether it’s inherited germline or de novo, whether it’s somatic and also its proximity to a gene. As a case in point, whole genome imaging has to date unraveled a number of genes never implicated in cancer and shown how they are affected by structural variations, along with deciphering novel structural variants. Hence, combining whole genome imaging with whole genome sequencing offers a strong integrative approach to understand small and large genomic variations in cancers.

For Research Use Only. Not for use in diagnostic procedures.