ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Oncogenic Addiction of Fibrolamellar Hepatocellular Carcinoma to the Fusion Kinase DNAJB1-PRKACA.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- Article
- Functional Precision Oncology in Fibrolamellar Carcinoma: Ex Vivo Identification of Therapeutic Vulnerabilities.Cancers · 2026Article
- Single-nucleus ATAC-seq analysis resolves chromatin and transcriptional features of fibrolamellar carcinoma.Scientific reports · 2026Article
- The GF-NEO discovery platform unveils a [KQE][DG] sequence motif within fusion neoantigens in pediatric cancer.iScience · 2026Article
- Article
- The latest progress of personalized drug screening and therapy research for common clinical tumors through the PDX model platform.Journal of pharmaceutical analysis · 2025Review
- Expression of DNAJB1-PRKACA oncogene suppresses the differentiation potential of liver progenitor organoids towards a hepatocyte lineage.Scientific reports · 2025Article
- Chemical Evolution of Aplithianine Class of Serine/Threonine Kinase Inhibitors.Journal of medicinal chemistry · 2025Article
- Mitochondrial calcium signaling regulates branched-chain amino acid catabolism in fibrolamellar carcinoma.Science advances · 2025Article
- Oncogenic gene fusions in cancer: from biology to therapy.Signal transduction and targeted therapy · 2025Review
- DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming.Cancer discovery · 2025Article
- Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma.Nature communications · 2024Article
- Therapeutic, Clinicopathological, and Molecular Correlates ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Targeted Degradation of Protein Kinase A via a Stapled Peptide PROTAC.ACS chemical biology · 2024Article
- Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- Increased Protein Kinase A Activity Induces Fibrolamellar Hepatocellular Carcinoma Features Independent of DNAJB1.Cancer research · 2024Article
- DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- DNAJB1-PRKACA fusion protein-regulated LINC00473 promotes tumor growth and alters mitochondrial fitness in fibrolamellar carcinoma.PLoS genetics · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeGene fusions are drivers of many pediatric tumors. In fibrolamellar hepatocellular carcinoma (FLC), a fusion of DNAJB1 and PRKACA is the dominant recurrent mutation. Expression of the DNAJB1-PRKACA fusion gene in mice results in a tumor that recapitulates FLC. However, it is not known whether transient expression of DNAJB1-PRKACA is sufficient only to trigger tumor formation or whether ongoing expression is necessary for maintenance and progression. EXPERIMENTAL
designWe screened short hairpin RNAs (shRNA) tiled over the fusion junction and identified several potent and specific candidates in vitro and two independent FLC patient-derived xenografts (PDX).
resultsWe show that continued DNAJB1-PRKACA expression is not only required for continued tumor growth, but additionally its inhibition results in cell death. Inhibition of DNAJB1-PRKACA by an inducible shRNA in cells of PDX of FLC resulted in cell death in vitro. Induction of the shRNA inhibits FLC tumors growing in mice with no effect on xenografts from a hepatocellular carcinoma cell line engineered to express DNAJB1-PRKACA.
conclusionsOur results validate DNAJB1-PRKACA as the oncogene in FLC and demonstrate both a continued requirement for the oncogene for tumor growth as well as an oncogenic addiction that can be exploited for targeted therapies. We anticipate our approach will be useful for investigations of other fusion genes in pediatric cancers and spur development of precision therapies.
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