{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:06:38Z","timestamp":1787501198968,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Division of Pediatric Surgery"},{"DOI":"10.13039\/100007172","name":"CCHMC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007172","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NT","award":["NIH R01 CA278834"],"award-info":[{"award-number":["NIH R01 CA278834"]}]},{"name":"AGM","award":["R01095001"],"award-info":[{"award-number":["R01095001"]}]},{"name":"Grace Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2019 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-\u03b2-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.<\/jats:p>","DOI":"10.3390\/cancers17010083","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T14:35:42Z","timestamp":1735742142000},"page":"83","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2313-6213","authenticated-orcid":false,"given":"Yasmeen","family":"Fleifil","sequence":"first","affiliation":[{"name":"Division of General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6194-9805","authenticated-orcid":false,"given":"Ruhi","family":"Gulati","sequence":"additional","affiliation":[{"name":"Division of General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Jennings","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Miethke","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology & Nutrition, Cincinnati Children Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-5948","authenticated-orcid":false,"given":"Alexander","family":"Bondoc","sequence":"additional","affiliation":[{"name":"Division of General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Tiao","sequence":"additional","affiliation":[{"name":"Division of General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James I.","family":"Geller","sequence":"additional","affiliation":[{"name":"Division of Oncology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0259-4550","authenticated-orcid":false,"given":"Rebekah","family":"Karns","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology & Nutrition, Cincinnati Children Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubov","family":"Timchenko","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Timchenko","sequence":"additional","affiliation":[{"name":"Division of General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"154655","DOI":"10.1016\/j.prp.2023.154655","article-title":"Exploring the molecular pathogenesis, diagnosis and treatment of fibrolamellar hepatocellular carcinoma: A state of art review of the current literature","volume":"248","author":"Alterity","year":"2023","journal-title":"Pathol. 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