Abstract 1020: A cancer patient survival study facilitated by an integrated enrichment workflow streamlined DNA and RNA sequencing of biopsy samples

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Abstract RNA sequencing provides valuable insights into gene expression alterations in response to drug-treatments, mutations, and gene fusions in cancer research. Combined analyses of RNA transcript variations and comprehensive genomic sequencing allows for cross-validation of somatic mutations, improvement of accuracy and clinical sensitivity, and understanding of the mutation effects on gene expression, yielding essential transcriptomic/genomic data that inform individual patient’s responses to therapeutic interventions. However, challenges in sample and library preparation, along with the complexity of conducting multiple target enrichments for RNA and DNA samples, often are costly and time consuming. In this research study, we employed the novel integrated target capture technology, TrinityTM, to simultaneously capture both RNA and DNA libraries in a single hybridization reaction, thereby streamlining the process and reducing overall costs. This optimized workflow significantly decreases sample-to-answer time below 21 hours, with 1 hour hybridization time and direct loading onto sequencing instrument. This improvement contrasts drastically to traditional multi-day procedures. Using this new approach, we processed matched DNA and RNA sequencing of blood and formalin-fixed paraffin-embedded (FFPE) tissue biopsy samples from eight prostate cancer patients collected pre- and post-intervention for treatment. As a result, the assay showed ∼ 10% higher mean target coverage at equivalent read depths compared to data generated from the same samples processed using conventional target capture workflow. Additionally, the coverage depth for Indels was significantly better and generated >0.99 Indel F1 scores with the exome panel in the benchmarking data of reference genome NA12878. Similarly, the RNA data obtained in the study increased sequencing efficiency and generated more usable RNA seq data than traditional bulk-RNA sequencing. We performed a comprehensive evaluation on intervention effect for treatment in both expression changes and mutation profiling and showed the feasibility to apply this assay to larger sample sizes. In summary, using TrinityTM for combined DNA/RNA hybrid capture workflow leads to a rapid, cost-effective workflow to simultaneously unlock both DNA and RNA biomarker insights. This advancement could accelerate multi-omic studies and contribute to research that could help the design of targeted therapies, ultimately benefiting the precision of cancer treatment. Citation Format: Junhua Zhao, Benjamin J. Krajacich, Kevin Green, Xiaodong Qi, Shawn Levy. A cancer patient survival study facilitated by an integrated enrichment workflow streamlined DNA and RNA sequencing of biopsy samples [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 1020.

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