Abstract 3242: Integrated long-read target enrichment and comprehensive genomic profiling for hematologic malignancies using the SureSelect Cancer Pan Heme assay

Abstract Next-generation sequencing (NGS) has transformed cancer research, yet its effectiveness is often constrained by sample quality, tumor fraction, and limitations inherent to short-read sequencing—particularly in detecting structural variants, complex rearrangements, and alterations in repetitive or polymorphic regions. Long-read sequencing offers a solution, but cost and throughput challenges persist. To address these limitations, we developed a flexible, automation-compatible library preparation and target enrichment workflow that supports DNA inputs down to 200 ng, accommodates both enzymatic and mechanical shearing, and enables fast hybridization (90 minutes). Coupled with long-read sequencing and the SureSelect Cancer Pan Heme assay, this platform enables detection of main genomic alterations—including SNVs, indels, CNVs, and gene fusions—within a single assay. The SureSelect Cancer Pan Heme panel, codeveloped with Roswell Park Comprehensive Cancer Center, interrogates 359 DNA and 124 RNA genes, delivering integrated DNA/RNA analysis and overcoming the limitations of conventional single-analyte methods such as karyotyping, FISH, and PCR. Although in this study, we only focus on DNA as the substrate. We demonstrate high enrichment efficiency using a novel fast hybridization buffer, achieving on-target rates >80% for libraries with insert sizes up to 4-5 kb. Comparative analysis versus short-read approaches reveals superior coverage in challenging genomic regions using enriched long-read sequencing as well as allowing to phase variants. This solution offers a cost-effective, scalable, and rapid-turnaround workflow for molecular laboratories, advancing precision oncology in hematologic malignancies. For Research Use Only. Not for use in diagnostic procedures. Citation Format: Brandyn Clark, Adam Janssen, Jeff Fox, Nedda Saremi, Kristi Stephenson, Kelle Hammock, Bahram Arezi. Integrated long-read target enrichment and comprehensive genomic profiling for hematologic malignancies using the SureSelect Cancer Pan Heme assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3242.