# 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 “Fleifil et al. DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways. Cancers 2025, 17, 83”

## TL;DR

This paper responds to a commentary about the presence of a DNAJB1::PRKACA fusion in pediatric liver cancers, confirming its absence in hepatoblastoma.

## Contribution

The paper provides a rebuttal confirming the fusion DNAJB1::PRKACA is not specific to hepatoblastoma, based on re-analysis of data.

## Key findings

- DNAJB1::PRKACA was detected in about 70% of HBL/HCN-NOS patients.
- The fusion remains specific to fibrolamellar carcinoma, not hepatoblastoma.
- The authors caution against using DNAJB1::PRKACA as a hepatoblastoma diagnostic marker without validation.

## Abstract

Arif and colleagues commented on our paper Fleifil et al. “DNAJB1-PKAc is expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways” 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 “…DNAJB1::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.” After reviewing the commentary, we are offering a response outlined below.