114. Comparison of optical genome mapping, CMA, and 523-gene NGS panel for Homologous Recombination Deficiency calculation

Aly Abdelkareem

Nikhil Sahajpal

Dr. Sahajpal is a post-doctoral fellow at Department of Pathology, Augusta University, GA, US, and an incumbent ABMGG Laboratory Genetics and Genomics Fellow at Greenwood Genetic Center, Greenwood, SC, USA.

Dr. Sahajpal is involved in investigating molecular and cytogenetic methodologies for prenatal, postnatal, hematological malignancies and solid tumor applications. Dr. Sahajpal is involved in multiple projects that include a) Clinical validation and utility of optical genome mapping for different clinical applications. b) Clinical validation and test development for the detection of SARS-CoV-2 virus, and sequencing the SARS-CoV-2 virus for phylogenetic modelling. c) Studying the host-genome susceptibility to SARS-CoV-2 via optical genome mapping. d) Application of Illumina’s TruSightOncology 500 (TSO500) for hematological malignancies and solid tumors. e) Application of ThermoFisher’s OncoScan Microarray platform for diagnostic utility in melanoma and brain tumors.


Nikhil Sahajpala, Ashis Mondala, Daniel Saulb, Soheil Shamsb, Alex Hastieb, Alka Chaubeyb, Ravindra Kolhea

aAugusta University, Augusta, GA, USA; bBionano Genomics, San Diego, CA, USA

Homologous Recombination Deficiency (HRD) is characterized by the inability of a cell to repair the double-stranded breaks using the homologous recombination repair (HRR) pathway. The deficiency of the HRR pathway results in defective DNA repair, leading to genomic instability and tumorigenesis. The presence of HRD has been found to make tumors sensitive to ICL-inducing platinum-based therapies and poly(adenosine diphosphate [ADP]?ribose) polymerase (PARP) inhibitors (PARPi). However, there are no standardized methods to define, measure, and report HRD in diagnostic laboratories. Herein, we compare optical genome mapping (OGM), chromosomal microarray (CMA), and 523-gene NGS panel for HRD scar calculations. Traditionally, CMA has been used to calculate either loss of heterozygosity (LOH), or a combination of LOH, telomeric allelic imbalance (TAI), and large scale transitions (LST), where a combination is more accurate than LOH score alone for HRD calculation. We demonstrate the use of a 523-gene NGS panel to detect HRD using NxClinical software with automated HRD calculation using LOH, TAI, and LST. More interestingly, we compare OGM with CMA and NGS panel and highlight the potential advantages of using OGM, which reveals the genomic instability with a much higher resolution compared to other methodologies. For example, in a case of glioblastoma, the HRD score with CMA was 7 (TAI:1, HRD-LOH: 2, LST: 4) compared to 29 with OGM (TAI:1, HRD-LOH:2, LST:25). The HRD definition, measurement, and reporting criteria need to be standardized for each platform, while OGM might be the most sensitive platform for HRD calculation.