Abstract 4412: Defining chromatin alterations in liver cancer at single cell resolution

Abstract

Abstract Hepatocellular carcinoma (HCC) is the most common liver cancer and arises from the malignant transformation of hepatocytes. HCC tumors often express genes critical for hepatocyte development but the regulatory mechanisms driving aberrant expression remain unclear. Recent evidence indicates that epigenetic alterations contribute to HCC progression with nearly 50% of cases associated with mutations in chromatin modifiers. Thus, it is imperative to understand how chromatin is altered in HCC and identify the DNA regulatory sequences associated with HCC tumorigenesis. Our study aims to map the chromatin landscape and transcriptome in HCC tumors using a multiomic approach at single cell resolution. Single-cell ATAC- and RNA-seq will be conducted in HCC tumors, matched controls and normal livers to identify regulatory sequences and their target genes critical for HCC tumor progression. We will characterize these regulatory sequences in the context of liver development using genetic manipulation and epigenomic datasets generated from human pluripotent stem cells differentiated to hepatic lineages. Our goal is to elucidate how epigenetic alterations in HCC drive cancer progression and how they relate to a dedifferentiated state. Citation Format: Miguel Ramirez, Tabea Stephan, Daivd Schaeffer, Pamela Hoodless. Defining chromatin alterations in liver cancer at single cell resolution [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 4412.