Abstract 455: Innovations in large scale liquid biopsy analysis and the Broad/IBM Cancer Resistance Project

Abstract

Abstract Broad Genomics offers a comprehensive liquid biopsy sequencing platform designed to provide the optimal flexibility for conducting research studies in a broad range of applications including: biomarker discovery, treatment resistance monitoring, and clinical grade ctDNA profiling. By utilizing low cost, low coverage whole genome sequencing in conjunction with dual unique molecular indexed (UMI) libraries we can offer a range of analysis that allow researchers to select the most appropriate samples for whole exome profiling or for deeper coverage, higher sensitivity targeted gene panels. To date we have generated over 3000 liquid biopsy whole genome copy number profiles and purity estimates and are supporting driver projects including the Broad/IBM Cancer Resistance Project and Count Me In. The study design for the Broad/IBM effort takes advantage of the discovery potential of tissue-based sequencing combined with serial liquid biopsy analysis to elucidate resistance events by tracking clonal and subclonal populations in patient samples over time. Sourcing samples for this and other similar efforts is a major undertaking and a combination of methods for maximally broad and deep genomic profiling are required to assay patients throughout the course of care, as tumor fraction in blood fluctuates. Responding to this need, and other applications requiring increased sensitivity we have developed a high throughput, automated workflow to efficiently assay cfDNA samples with lower tumor content. Benchmarking data using healthy donor pooled cfDNA samples indicates our assay is capable of detecting > 90% of variants present at ~1% minor allele fraction with less than 1 false positive variant called per megabase. This established laboratory and analytic process forms the basis of our 2Mb, 400 gene CLIA targeted assay currently undergoing validation. Through this suite of products we hope to enable an expansion of cfDNA sequencing efforts in support of clinical and research applications. Early results from emerging studies utilizing this platform to be presented. Citation Format: Carrie Cibulskis, Brendan Blumenstiel, Matthew DeFelice, Mark Fleharty, Justin Abreu, Viktor Adalsteinsson, Laxmi Parida, Susanna Hamilton, Gad Getz, Niall Lennon. Innovations in large scale liquid biopsy analysis and the Broad/IBM Cancer Resistance Project [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 455.