{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:13:27Z","timestamp":1787235207721,"version":"build-2736575974"},"reference-count":12,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Arif and colleagues commented on our paper Fleifil et al. \u201cDNAJB1-PKAc is expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways\u201d published in Cancers in 2024. In our paper, we examined expression of DNAJB1::PRKACA (DNAJB1-PKAc or J-PKAc) in the Bio Bank of HBL (Hepatoblastoma) and HCN-NOS (Hepatocellular Malignant Neoplasm, Not Otherwise Specified) tissue samples collected at CCHMC during the last five years. Our data demonstrated that DNAJB1::PRKACA was detected in approximately 70% of HBL\/HCN-NOS patients, with varying expression levels. In the commentary, the authors reviewed their earlier data and found no evidence of the fusion DNAJB1-PKAc expression within their cohorts of HBL specimens. Based on these data, the authors stated that \u201c\u2026DNAJB1::PRKACA remains specific to fibrolamellar carcinoma among liver tumors and caution against its use as a diagnostic marker for hepatoblastoma without rigorous validation in external cohorts.\u201d After reviewing the commentary, we are offering a response outlined below.<\/jats:p>","DOI":"10.3390\/cancers18060918","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:46:31Z","timestamp":1773326791000},"page":"918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fusion DNAJB1::PRKACA in Non-Fibrolamellar Cancer Cases. Reply to Arif et al. Global Re-Analysis Confirms Absence of the DNAJB1::PRKACA Fusion in Hepatoblastoma. Comment on \u201cFleifil et al. DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways. Cancers 2025, 17, 83\u201d"],"prefix":"10.3390","volume":"18","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"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7450-4248","authenticated-orcid":false,"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\u2019s Hospital Medical Center, 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"}]},{"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\u2019s 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":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fleifil, Y., Gulati, R., Jennings, K., Miethke, A., Bondoc, A., Tiao, G., Geller, J.I., Karns, R., Timchenko, L., and Timchenko, N. (2025). DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways. Cancers, 17.","DOI":"10.3390\/cancers17010083"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Arif, W., Simon, S.M., O\u2019Neill, A.F., Putra, J., L\u00f3pez-Terrada, D.H., Yarchoan, M., Zucman-Rossi, J., and Hirsch, T.Z. (2026). Global Re-Analysis Confirms Absence of the DNAJB1::PRKACA Fusion in Hepatoblastoma. Comment on Fleifil et al. DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways. Cancers 2025, 17, 83. Cancers, 18.","DOI":"10.3390\/cancers18050877"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1053\/j.gastro.2019.10.028","article-title":"Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct","volume":"158","author":"Singhi","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_4","first-page":"475","article-title":"The Use of Fluorescence in situ Hybridization to Confirm PRKACA Gene Rearrangement in Fibrolamellar Hepatocellular Carcinoma: A Validation Study","volume":"52","author":"Weiel","year":"2022","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/s41379-022-01068-w","article-title":"Low-grade non-intestinal type sinonasal adenocarcinoma: A histologically distinctive but molecularly heterogeneous entity","volume":"35","author":"Rooper","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/s41379-019-0398-2","article-title":"DNAJB1-PRKACA fusions occur in oncocytic pancreatic and biliary neoplasms and are not specific for fibrolamellar hepatocellular carcinoma","volume":"33","author":"Vyas","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100358","DOI":"10.1016\/j.modpat.2023.100358","article-title":"Gene Rearrangement and Expression of PRKACA and PRKACB Govern Morphobiology of Pancreatobiliary Oncocytic Neoplasms","volume":"37","author":"Itoh","year":"2024","journal-title":"Mod. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100554","DOI":"10.1016\/j.modpat.2024.100554","article-title":"Comprehensive Characterization of Intraductal Oncocytic Papillary Neoplasm of the Pancreas: A Systematic and Critical Review","volume":"37","author":"Paolino","year":"2024","journal-title":"Mod. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s00428-022-03415-3","article-title":"Investigation of -PRKACA\/-PRKACB fusion genes in oncocytic tumors of the pancreatobiliary and other systems","volume":"481","author":"Maimaitiali","year":"2022","journal-title":"Virchows Arch."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/s12957-025-03997-7","article-title":"Deciphering pancreatobiliary intraductal oncocytic papillary neoplasms: Integrative analysis of histomorphologic patterns, immunophenotypic markers, and emerging molecular biomarkers","volume":"23","author":"Qian","year":"2025","journal-title":"World J. Surg. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1002\/hep.29719","article-title":"Fibrolamellar Carcinoma in the Carney complex: PAKAR1aA loss instead of the classic DNAJB1-PRKACA fusion","volume":"68","author":"Graham","year":"2018","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1158\/0008-5472.CAN-23-4110","article-title":"Increased Protein Kinase A Activity Induces Fibrolamellar Hepatocellular Carcinoma Features Independent of DNAJB1","volume":"84","author":"Shirani","year":"2024","journal-title":"Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/6\/918\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:10:26Z","timestamp":1773328226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/6\/918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":12,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["cancers18060918"],"URL":"https:\/\/doi.org\/10.3390\/cancers18060918","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]}}}