Bionano Genomics, Inc. announced a peer-reviewed publication in Cancers from a team of cancer researchers primarily at the NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute and Scripps MD Anderson in La Jolla, California. The publication describes what could be the first study to use optical genome mapping (OGM) for the discovery of structural variants (SVs) that drive drug resistance and sensitivity in cancer.  Study Design: Patient Samples. The study analyzed 26 leukemia samples from 23 subjects, including 3 samples from subjects after relapse.

Genome Variation Signatures. The study compared genome variation signatures obtained from the leukemia samples by OGM and by classical cytogenetic methods including karyotyping (KT) and fluorescence in situ hybridization (FISH). Drug Library.   The study used a broad collection of 120 cancer drugs based on the Oncology Drug Library (ODL, ODL2 and ODL3) and the FDA-approved oncology collection drugs from the NCI?s Developmental Therapeutics Program, including some experimental agents and those in phase II/III trials.

Drug Resistance & Sensitivity Assay. The study used a cell viability and drug screening assay based on growing leukemia-enriched cell collections in the presence of different concentrations of drug agents to measure cell viability. Cells that grew well in the presence of drugs were determined to be resistant and those that didn?t were determined to be sensitive.

Overall, the study shows that OGM for SV detection combined with drug sensitivity data for the same samples is a useful approach to identifying potentially pathogenic SVs that may be drivers of drug sensitivity or resistance. Key findings are as follows: OGM detected all SVs that had been observed using classical cytogenetic methods as well as multiple additional variants that were not previously reported, BCR-ABL1 translocated leukemia samples are sensitive to the tyrosine kinase inhibitor Nilotinib, as expected, but exhibit resistance to proteasome inhibitors, Drug sensitivities associated with previously unreported genomic rearrangements were revealed, Leukemia samples with KMT2A translocations are associated with drug sensitivities to the microtubule disruptors Paclitaxel and Cabazitaxel and resistance to Bcl-2 family inhibitors, Chemosensitivity associations with SVs detected by OGM are able to reveal several potential new treatment strategies for leukemia.