Abstract 4080: A novel integrated target capture and rapid sequencing workflow for myeloid malignancy mutation detection within 12 hours

Abstract Hybrid capture technology is a powerful and cost-effective tool in precision oncology research to detect somatic mutations in hematologic malignancies. While target capture is important for efficient mutation detection, obtaining rapid sequencing results is critical for research in this field. Traditional hybrid capture workflows involve several time-consuming steps prior to sequencing, including post-hybridization capture, washes, and amplification, which can delay results. Here, we combine Trinity™ hybrid capture and a rapid AVITI™ sequencing protocol to deliver targeted sequencing results within 12 hours. We applied this rapid Trinity™ workflow together with a custom myeloid panel based on a design used by Genomics Medicine Sweden to detect mutations in reference DNA and patient blood/bone marrow/fresh frozen tissue. This custom panel builds on an earlier design, targeting genes included in contemporary guidelines and those with strong or potential clinical impact as well as genes reported in the literature but with less established clinical relevance. The final 7,901-probe panel spans a target region of 0.73 kb and provides uniform coverage across all targets, including challenging GC-rich regions. We were able to detect myeloid malignancy mutations between 0.5%-70% VAF in Horizon’s Mimix™ Myeloid DNA Reference Standard, including internal tandem duplications observed in some patients with acute myeloid leukemia (AML). In sum, the Trinity™ workflow on the AVITI™ sequencer provides a rapid, accurate, and robust solution for targeted sequencing, offering significant advancements in turn-around time for hematology malignancy research. Citation Format: Kyle S. Metcalfe, Benjamin J. Krajacich, Xiaodong Qi, Kelly Wiseman, Marina McCowin, Shawn Levy, Junhua Zhao. A novel integrated target capture and rapid sequencing workflow for myeloid malignancy mutation detection within 12 hours [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4080.