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Cancer Genomics: Heme Malignancies and
Solid Tumor Research

To get a complete picture of highly rearranged cancer genomes in heterogeneous samples, you need long-range information at high coverage and analysis tools with high sensitivity and specificity. Bionano optical genome mapping (OGM) routinely collects up to 400x coverage of a human genome to uncover large structural variations beyond what short- and long-read sequencing can see, at 5% variant allele fraction.

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Unbiased, Genome-wide SV Detection for Complex Cancer Samples

Cancer samples are too complex for low-coverage whole genome sequencing. Complex rearrangements, tumor heterogeneity and unsequenceable repetitive regions of the genome present additional challenges for short- and long-read sequencing technologies.

The Bionano Saphyr^® System detects structural variations in an unbiased manner at much higher sensitivities than sequencing-based technologies, and routinely at 5% variant allele fraction.

Find the Right Solution for Optical Genome Mapping

Our tools and platforms provide unparalleled structural variation detection for cancer research.

Data Examples

Explore how optical genome technology works

See variants in GC rich regions

Identify mutations without complex pipelines

Stratify samples easily

Identify rare and new fusions of known genes

The OGM workflow starts with mega-base size DNA isolation. A single enzymatic reaction labels the genome at a specific sequence motif occurring approximately 15 times per 100 kbp in the human genome. The long, labeled DNA molecules are linearized in nanochannel arrays on a Saphyr Chip^® and imaged in an automated manner by the Saphyr Instrument. Using pairwise alignments, the molecules are assembled into local maps or whole genome de novo assemblies. Changes in patterning or spacing of the labels are detected automatically, genome-wide, to call all structural variants.

In a patient-derived model of uveal melanoma, no pathogenic variant or epigenetic event was found explaining the loss of expression of gene 1 using NGS, which is typically associated with this cancer. OGM identified a 740 bp deletion in the promoter of gene 1. This region was missed by sequencing due to the high GC content of that region.

Gentien D, Saberi-Ansari E, Servant N, et al. Multi-omics comparison of malignant and normal uveal melanocytes reveals novel molecular features of uveal melanoma. bioRxiv 2022.03.11.483767; doi: https://doi.org/10.1101/2022.03.11.483767.

Cancer samples often display a high number of structural rearrangements or changes and the limitation caused by the short-read length of NGS is particularly detrimental for correctly reconstructing these chained fusion events. In this patient-derived breast cancer cell line, a consensus map resulting from the alignment of dozens of molecules spanning the region allowed OGM to identify a succession of a translocation, deletions and an inversion missed by short-read and long read-sequencing.

The ability to stratify patient samples based on mutational profile usually requires extensive bioinformatic data curation downstream of sequencing. In a hepatocellular carcinoma study, our built-in pipeline automatically provides enough information to distinguish samples with or without a replication stress signature, resulting from a Hepatitis B Virus insertion 9 kb upstream of the Cyclin E1 gene. With the development of innovative therapies such as PARP inhibitors, patient stratification based on accumulation of DNA damage is critical.

Péneau C, Imbeaud S, La Bella T, et al. Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocellular carcinoma. Gut. 2022;71(3):616-626. doi: 10.1136/gutjnl-2020-323153.

In a large systematic comparative study between OGM and classical cytogenetics, OGM identified novel, non-recurrent fusions never reported before. In both cases shown here, one of the two fusion partners is well known in leukemia as a gene fusion. These events were missed by classical cytogenetics either because of their low allelic frequencies or because of the targeted FISH approach classically used in a diagnostics context.

Neveling K, Mantere T, Vermeulen S, et al. Next-generation cytogenetics: Comprehensive assessment of 52 hematological malignancy genomes by optical genome mapping. Am J Hum Genet. 2021;108(8):1423-1435. doi: 10.1016/j.ajhg.2021.06.001.