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Samuel Brody



Job Title

Technical Research Assistant II

Academic Rank




Samuel J. Brody, Adrian M. Dubuc

Principal Investigator

Adrian M. Dubuc

Research Category: Cancer


Optical Genome Mapping Unmasks ‘Chromosomal Mimicry’ and Improves Detection of Actionable Structural Variants in Leukemias

Scientific Abstract

With the discovery of the Philadelphia (Ph+) chromosome and identification of BCR::ABl1, detection of structural variants using traditional cytogenetic techniques has become an essential component in the diagnostic evaluation of hematologic malignancies. Analysis of this class of alteration relies on visual assessments of chromosome morphology, which suffers from limited resolution precluding accurate detection of clinically important variants. A recent advancement, Optical Genomic Mapping (OGM) is a novel technology that fluorescently labels hexamer sequences from large fragments of genomic DNA (>150 kilobases), images linearized DNA molecules and maps them against a reference genome. OGM is fast, quickly learned, and can readily achieve 500 base pair resolution and 400x genome-wide coverage, far exceeding the scale and sensitivity offered by standard-of-care testing. OGM profiling of a cohort (n=20) of leukemias detected actionable in-frame gene fusions and enhancer hijacker events. OGM also revealed rare but recurrent instances of “chromosomal mimicry”, in which chromosome morphology mimicked important structural variants which were subsequently refuted by OGM analysis. Our work highlights the potential of OGM as a novel and improved diagnostic assay with the capacity to ameliorate detection of clinically relevant structural variants.

Lay Abstract

Genetic studies have become an increasingly critical component in the delivery of care for patients with cancer. For many blood-based cancers, the visual analysis of chromosomes – thread-like structures inside the nucleus made of tightly packed DNA – is necessary to achieve a final diagnoses or guide treatment. Optical Genome Mapping (OGM) is a new technology which has the capacity to revolutionize the detection of chromosomal changes with significantly greater resolution that previous approaches thus improving diagnostic evaluations, and potentially leading to the discovery of new therapy targets. OGM analysis across a series of patients with leukemias demonstrated the power of this technology to improve detection of clinically important changes.

Clinical Implications

Optical Genome Mapping improves the diagnostic evaluation of structural variants in hematologic malignancies with greater sensitivity and specificity than standard-of-care approaches. It generates an assessment of the structural landscape of genomes with the potential for discovery of novel therapeutic vulnerabilities.