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A team led by Dr. Alexander Hoischen from Radboud University Medical Center (RUMC) in the Netherlands reported the results of a successful validation study comparing the performance of Bionano Genomics’ Saphyr® system to traditional cytogenetic methods for the clinical analysis of leukemia genomes. The study, published in bioRxiv, found that Saphyr was 100% concordant with the standard of care for the detection of somatic chromosomal abnormalities.

Structural variants are important for cancer diagnosis, prognosis, and treatment decisions. In a diagnostic set-up, especially for hematological malignancies, the comprehensive analysis of all cytogenetic aberrations requires a combination of techniques, such as karyotyping, fluorescence in situ hybridization and CNV-microarrays. The study set out to test if optical genome mapping (OGM) by the Saphyr system could replace these expensive, labor-intensive and time-consuming combination of methods with a single, automated and streamlined workflow.

A total of 48 patient samples with a combination of myeloid and lymphoid leukemias, representative of the most common referrals to the RUMC clinic, were analyzed using standard cytogenetic analysis. All samples had an allele fraction of the pathogenic variants of at least 10%. 37 samples were considered simple and 11 samples were categorized as complex, based on the number of large structural abnormalities. When all 48 samples were subsequently analyzed with Bionano, the team was able to identify all previously reported aberrations. Bionano allowed for a better resolution and a more complete picture of complex aberrations. Acomplex chromothripsis structure was resolved unambiguously and in other cases, additional fusions were identified, or marker chromosomes of unknown origin were resolved. Generally, OGM results were more complete than all three individual previous tests and most likely delivered the true underlying genomic architecture.

The Radboud team pointed out that while the focus of the study was on determining the concordance for diagnostically reported variants, the Bionano technology also found novel variants. They identified 23 potential gene fusions of which only 4 were previously observed. Gene fusions are important prognostic markers in cancer and are routinely targeted for drug development. The Bionano study provided an impressive number of such potential biomarkers.

Alexander Hoischen, Ph.D., Associate Professor, Genomic Technologies and Immuno-Genomics at the Department of Human Genetics of RUMC, commented: “We are positively surprised by the smooth and fast implementation of the Saphyr system in our laboratory. Less than a year after training we now have successfully run more than 150 samples, including the 48 leukemia samples which we now present in this publication. Other samples include novel research findings for unsolved rare disease cases and known cytogenetic abnormalities which may validate the Saphyr system’s use for constitutional aberrations. We are excited about the very high concordance rate between Bionano technology and current standard of care methods and believe that this technology has the potential to revolutionize cytogenetics in the near future.”

Erik Holmlin, Ph.D., CEO of Bionano, commented, “At Bionano, our objective has been to develop the best genome analysis platform to identify structural variation, and it has long been a focus of ours to apply that capability for clinical diagnostics. We have focused on leukemias and lymphomas because the current standard of care consists of a complex combination of various outdated methods, and diagnostic labs, clinicians and patients would be better off if that was transformed. Many attempts have been made to replace cytogenetics using various flavors of short-read and long-read sequencing, and all have failed. This study helps confirm that our Saphyr platform is capable of revolutionizing cytogenetic testing and is the first of many such studies that we believe will demonstrate this utility.”

Read the study on bioRxiv.



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