2. Analytical tools to support detection of homologous recombination deficiency (HRD) using cytogenomic scar markers

Homologous Recombination Deficiency (HRD) has been shown to be an effective pharmacogenetic biomarker for determining the efficacy of PARP inhibitor therapy across various tumor types. There is continued research on the best approach to measure HRD status including assessments of sequence variants of homologous recombination repair pathway genes and consequential patterns of genomic instability.  Recent technological advancements have enabled for more robust measurement of the cytogenomic aberrations associated with genomic instability emphasizing the importance of its analysis for HRD. Various publications have defined multiple “genomic scars” to determine HRD genomic instability and it has been further reported that a combined analysis of these genomic scars can offer a better estimate of HRD status of the tumor. In this presentation, we will provide a review of the current evidence on HRD genomic instability as a pharmacogenomic marker, describe the various cytogenomic and molecular methods for detection of genomic scars, and highlight challenges and solutions for measuring these genomics scars using available software tools. We also will introduce a new analysis approach for analysis of genomic instability which enables a more robust assessment of genomic scars across various technology types that enables comprehensive scoring of HRD status. We will demonstrate how such measurements can be made from various genomic techniques including chromosomal SNP microarrays, cancer specific NGS panels, as well as Optical Genome Mapping (OGM) using example cases processed on differing platforms to provide insight to the relative advantages for an analysis of genomic instability.