Abstract 6085: Leveraging targeted epigenetic and genetic detection for cost-effective cancer classification

Abstract The combinatorial power of genetics and epigenetics is vital to understanding biology in healthy and cancerous states. Utilizing a recent novel approach, we enable the simultaneous identification of modified cytosine and the canonical bases A, C, T & G in an enzymatic single-workflow solution. Generating this information across the whole genome provides a much-improved understanding of genetic and epigenetic changes, but can require a large amount of sequencing, particularly when exploring at depth. Enrichment protocols such as target enrichment enable deep interrogation of target areas whilst maintaining cost effectiveness. Target enrichment panels enable the selective isolation of sequences of interest through target hybridization. Using commercially available panels combined with the novel enzymatic single-workflow solution we show uniform performance across a range of input amounts with reduced sequencing requirements. Samples used were cell free DNA (cfDNA) from patient samples with either Stage I or IV Colorectal Cancer and reportedly healthy controls and were targeted using pan-cancer and methylome panels. Widespread differences such as hypermethylation are clearly observed in late-stage cancer vs early-stage or healthy controls demonstrating utility of the approach for applications such as liquid biopsy. Refining genetic and epigenetic investigations to a narrower region of interest can improve detection of low prevalence disease associated biomarkers at significant sequencing depth and lower sequencing costs. Citation Format: Robert Crawford, Ben Krajacich, Ermira Lleshi, Aurel Negrea, Lisabet Andreasen, Jens Fullgrabe, Jack Monahan, David Morley, Fabio Puddu, Donna McDade Walker, Semyon Kruglyak, Páidí Creed. Leveraging targeted epigenetic and genetic detection for cost-effective cancer classification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6085.