Abstract 338: Unraveling layers of proteogenomic complexity in cancer through multiomic exploration of archived FFPE tissue

Abstract

Abstract Formalin Fixed Paraffin Embedded (FFPE) tissues are a staple in clinical diagnostics associated with solid tumor. The preserved tumor tissue can be interrogated using classical histopathology and complemented with molecular approaches to elucidate cancerous SNPs, indels, structural variants, repeat expansion, copy number expansions, and mutational burden. Increasingly, approaches are being deployed to interrogate tissue not only through individual datasets but through integrated approaches that provide spatial information that defines the tumor microenvironment. Here, we illustrate using FFPE blocks from various tissues a multiomic workflow that allows for deep exploration of the molecular underpinnings of cancerous tissue. FFPE blocks were serially sliced into various FFPE slides with a single slide H&E stained. Individual slides were then utilized to explore the genome, epigenome, single cell RNA-seq, and digital spatial profiling. Genome information was captured using hybrid capture based approaches (whole exome sequencing and targeted cancer panel) followed by deep NGS on an Illumina platform and analyzed for a variety of variants and tumor mutational burden. DNA methylation was detailed using target capture probes targeting DNA methylation sites. Single cell approaches were applied to explore the transcriptome using 10X Genomics scRNAseq Flex kit. Digital spatial profiling was done using the NanoString for both transcriptomics and proteomics, with the GeoMx Whole Transcriptome Atlas and Human Core and Pan-Tumor protein panels. Aggregating these data illustrates the expanding landscape of information that can be extracted from FFPE derived tissue and the potential for novel discovery and diagnostic power integrating these complex data types holds. Citation Format: Andrea J. O'Hara, Yang Han, Ilaria DeVito, Laure Turner, Haythem Latif. Unraveling layers of proteogenomic complexity in cancer through multiomic exploration of archived FFPE tissue [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 338.