Chemical, molecular, and single cell analysis reveal chondroitin sulfate proteoglycan aberrancy in fibrolamellar carcinoma

Fibrolamellar carcinoma (FLC) is an aggressive liver cancer that predominantly afflicts adolescents and young adults. Patients with FLC are characterized by a heterozygous deletion on chromosome 19 that creates an oncogenic gene fusion, DNAJB1-PRKACA. The extracellular environment of FLC tumors is poorly characterized and may contribute to cancer progression, metastasis, and/or drug resistance. To bridge this knowledge gap, we propose to assess pathways relevant to proteoglycans, a major component of the extracellular matrix. We leveraged single-cell ATAC-seq to analyze the diversity of VCAN accessibility across different cell types. Human primary tumor and adjacent nonmalignant liver samples were resected and flash frozen. We used single cell ATAC-seq to assess genome accessibility across three types of samples; non-malignant liver (n=2), primary fibrolamellar carcinoma tumor (n=2), and metastatic fibrolamellar carcinoma (n=2).