{"doi":"10.3390/cancers17010083","title":"DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways","abstract":"Background and Aims: Hepatoblastoma (HBL) and fibrolamellar hepatocellular carcinoma (FLC) are the most common liver malignancies in children and young adults. FLC oncogenesis is associated with the generation of the fusion kinase, DNAJB1-PKAc (J-PKAc). J-PKAc has been found in 90% of FLC patients’ tumors but not in other liver cancers. Since previous studies of J-PKAc were performed with adolescent patients, we asked if young children may express J-PKAc and if there are consequences of such expression. Methods: The biobank of the pediatric HBL/HCN-NOS specimens was examined by QRT-PCR, Western blots, RNA-Seq, and immunostaining with fusion-specific antibodies. Results: J-PKAc is expressed in 70% of the HBL/HCN-NOS patients. RNA-Seq analysis revealed that HBL tumors that do not have cells expressing J-PKAc show elevated expression of the membrane attack complex (MAC), which eliminates cells expressing J-PKAc. The fusion-positive HBL/HCN-NOS samples have several signaling pathways that are different from fusion-negative HBLs. Upregulated pathways included genes involved in the G1 to S transition and in liver cancer. Downregulated pathways included over 60 tumor suppressors, the CYP family, and the SLC family. The repression of these genes involves J-PKAc-β-catenin-TCF4-mediated elevation of the HDAC1-Sp5 pathway. The identified upregulated and downregulated pathways are direct targets of the fusion kinase. The J-PKAc kinase is also detected in livers of 1-year-old children with biliary atresia (BA). Conclusions: J-PKAc is expressed in both HBL tumor and BA liver samples, contributing to the development of HBL and creating a transcriptome profiling consistent with the potential development of liver cancer in young patients.","journal":"Cancers","year":2024,"id":452129,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9659,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":692819,"name":"Ruhi Gulati","orcid":"0000-0002-6194-9805","position":1,"is_corresponding":false},{"id":1273971,"name":"Katherine M. Jennings","orcid":"0000-0003-3708-3973","position":2,"is_corresponding":false},{"id":286721,"name":"Alexander Miethke","orcid":"0000-0003-1395-9475","position":3,"is_corresponding":false},{"id":668483,"name":"Alexander Bondoc","orcid":null,"position":4,"is_corresponding":false},{"id":668484,"name":"Gregory M. Tiao","orcid":null,"position":5,"is_corresponding":false},{"id":342739,"name":"James I. Geller","orcid":"0000-0001-5181-116X","position":6,"is_corresponding":false},{"id":1273972,"name":"Rebekah Karns","orcid":"0009-0007-0259-4550","position":7,"is_corresponding":false},{"id":693363,"name":"Lubov Timchenko","orcid":null,"position":8,"is_corresponding":false},{"id":692821,"name":"Nikolai A. Timchenko","orcid":"0000-0003-4827-8274","position":9,"is_corresponding":false},{"id":908208,"name":"Yasmeen Fleifil","orcid":"0009-0001-2313-6213","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:02:50.407779Z","pmid":"39796711","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}