Evidence map›Paper›PMID 42650017›Full record

ArticleCancers2026

Detection of Low Levels of DNAJB1::PRKACA Fusion KinaseRequires the Utilization of Sensitive Assays and CarefulMethodological Planning. Reply to Palaz et al. Independent Multi-Cohort RNA-Seq Analysis Does Not Support Recurrent DNAJB1::PRKACA Fusion in Hepatoblastoma or Biliary Atresia. Comment on "Fleifil et al. DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways.

Yasmeen Fleifil, Ruhi Gulati, Katherine Jennings, Alexander Miethke, Alexander Bondoc, Gregory Tiao, Rebekah Karns, Lubov Timchenko, Nikolai Timchenko

Abstract readComment
In one paragraph

Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Yasmeen FleifilDivision of General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.ORCID 0009-0001-2313-6213
Ruhi GulatiDivision of General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.ORCID 0000-0002-6194-9805
Katherine JenningsDepartment of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.ORCID 0009-0009-7450-4248
Alexander MiethkeDepartment of Gastroenterology, Hepatology & Nutrition, Cincinnati Children Hospital Medical Center, Cincinnati, OH 45229, USA.ORCID 0000-0003-1395-9475
Alexander BondocDivision of General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.ORCID 0000-0002-9802-5948
Gregory TiaoDivision of Abdominal Transplantation, Stanford University, Palo Alto, CA 94304, USA.
Rebekah KarnsDepartment of Gastroenterology, Hepatology & Nutrition, Cincinnati Children Hospital Medical Center, Cincinnati, OH 45229, USA.ORCID 0009-0007-0259-4550
Lubov TimchenkoDepartment of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Nikolai TimchenkoDivision of General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Funding

The role of DNAJB1-PKAc-β-catenin axis in fibrolamellar HCCR01CA278834 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI Soona Shin · 2023 to 2026
$2.5M
NCI NIH HHS R01 CA278834
6 · The paper itself

Abstract

In 2024, we published a paper which described the identification of the fusion DNAJB1::PRKACA kinase in young patients with aggressive hepatoblastoma (HBL) and with biliary atresia (BA). In our study, we used sensitive molecular and cellular techniques and found that about 70% of our analyzed HBL samples showed varying levels of DNAJB1::PRKACA expression. In total, 15-20% of those fusion-positive HBL samples had DNAJB1::PRKACA levels comparable to those observed in FLC, whereas the remaining samples exhibited lower kinase levels. Palaz et al. analyzed five HBL datasets and one BA RNA-Seq dataset with Arriba and found no DNAJB1::PRKACA fusion transcript. Based on their analysis, the authors concluded that DNAJB1::PRKACA is not expressed in HBL patients. They further stated that the identification of DNAJB1::PRKACA fusion in either HBL or BA requires orthogonal molecular validation to confirm the fusion event at the DNA or RNA level. Therefore, we conducted Sanger sequencing on RT-PCR products from several fusion-positive HBL samples and three BA samples. Both HBL and BA cases showed the presence of the DNAJB1::PRKACA fusion transcript, identical to that detected in FLC. These results verify that DNAJB1::PRKACA is present in some HBL and BA patients, as has already been demonstrated using sensitive molecular and cellular techniques. Arriba analysis of current RNA-Seq data may not be sensitive enough for detecting low DNAJB1::PRKACA levels in HBL cases, especially if they are mixed with fusion-negative HBL specimens. Thus, we found that several independent methods, such as immunoanalysis and RT-PCR sequencing, effectively detect DNAJB1::PRKACA in HBL and BA cases. Our study also highlights that detecting low levels of DNAJB1::PRKACA requires individual analysis of HBL and BA patients within the same study, using FLC as the control.

Indexed as

biliary atresiaDNAJB1::PRKACAfibrolamellar HCChepatoblastoma

Identifiers

PMID42650017
PMCPMC13511183

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.