{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305096/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305096"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"DNAJ-PKAc Induces Metabolic Rewiring and a Glutamine Dependency in Fibrolamellar HCC","description":"Background: Fibrolamellar carcinoma (FLC) is a pediatric and adolescent liver cancer that is characterized by a recurrent fusion of DNAJB1 and PRKACA, yielding a chimeric translated protein, DNAJ-PKAc. PRKACA encodes the catalytic subunit of protein kinase A (PKA), a regulator of cellular metabolism. Methods: We generated a syngeneic murine model of FLC, TIBx-DNAJ-PKAc. We utilized preclinical models of FLC and human specimens to characterize the metabolic and immune effects of DNAJ-PKAc. Results: DNAJ-PKAc induced a high glycolytic flux and glutamine dependence to support nucleotide metabolism and redox homeostasis. TIBx-DNAJ-PKAc tumors demonstrated reduced T cell infiltration with impaired T cell activation. Systemic administration of a glutamine antagonist reversed the immune-inactivated phenotype of TIBx-DNAJ-PKAc tumors and provided durable control in combination with immune checkpoint inhibitors (ICI). Conclusion: The presence of DNAJ-PKAc creates a vulnerability to the combination of glutamine antimetabolite and ICI therapy in FLC.","dates":{"publication":"2026/05/15"},"accession":"GSE305096","cross_references":{"GSM":["GSM9162200","GSM9162202","GSM9162201","GSM9162204","GSM9162203","GSM9162205"],"GPL":["24247"],"GSE":["305096"],"taxon":["Mus musculus"],"PMID":["[41205756]"]}}