Fibrolamellar Cancer Foundation

CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates that the DNAJB1-PRKACA Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma

The DNAJB1-PRKACA fusion gene is found in almost all FLC tumors. In order to determine if this gene fusion is a cause of the tumors, these researchers used a CRISPR-Cas9 technique to create a chimeric DNAJB1-PRKACA fusion gene in the livers of otherwise healthy mice. Using the CRISPR-Cas9 system, the researchers created guide RNAs that …

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study

In this study, researchers reviewed the detailed medical records of 262 patients under age 20 diagnosed with liver cancers, assembled from 19 different hospitals and covering the years 1990 to 2017. This represents the richest available source of data on these pediatric liver cancers. They found that 119 (45%) of the tumors had been classified …

Multi-omic analysis of microRNA-mediated regulation reveals a proliferative axis involving miR-10b in fibrolamellar carcinoma

Nearly all FLC tumors carry the fusion gene DNAJB1-PRKACA and the expressed protein chimera DNAJ-PKAc which is believed to be the driver of FLC formation. However, to identify potential new therapies for FLC, it is important to understand the specific mechanisms that drive the progression of the disease. In a previous study, the Sethupathy lab …

Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss

“Organoids,” three-dimensional cell cultures that mimic critical features of normal human organs, are a novel tool to study fundamental steps in the development of cancers. The authors of this paper, a team from Utrecht, The Netherlands, wanted to understand how specific genetic alterations contribute to the transformation of normal liver cells into fibrolamellar carcinoma (FLC). …

DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma

In this study, published in March 2024, the researchers looked at how a patient’s immune system responds to the protein produced by the fusion of the genes DNAJB1 and PRKACA in FLC. Specifically, the team aimed to understand how the immune system’s “killer” T cells (CD8s) respond to this mutation and evaluate T cell receptors …

The genomic landscape of fibrolamellar hepatocellular carcinoma: whole genome sequencing of ten patients

This study sequenced the DNA from FLC tumors and compared the results to the DNA from non-cancerous tissue from the same patients to identify the specific mutations that had occurred in the cancer. In the 10 samples examined, the only consistent mutation was the DNAJB1-PRKACA fusion gene. Since the only consistent mutation found was the …

Clinical and demographic predictors of survival for fibrolamellar carcinoma patients—A patient community, registry‐based study

This study looked for associations between demographic, clinical factors and overall survival using data from the Fibrolamellar Registry. Several key findings emerged: In conclusion, while this study provides insights into factors associated with survival in FLC patients, further research is needed to better understand this rare cancer. The full text of the publication can be …

Molecular testing for the clinical diagnosis of fibrolamellar carcinoma

Historically, fibrolamellar carcinoma (FLC) has been diagnosed by analyzing the histology (microscopic anatomy) and morphology (shape, size and structure) of the tumor tissue. Frequently, that examination is combined with immunostaining for cytokeratin 7 and CD68. That immunostaining uses antibodies to see if proteins typically found in FLC are present. However, accurate diagnosis of fibrolamellar carcinoma …

An acquired scaffolding function of the DNAJ-PKAc fusion contributes to oncogenic signaling in fibrolamellar carcinoma

Fibrolamellar carcinoma (FLC) is driven by the fusion protein DNAJ-PKAc. That protein is made up of two different parts, one that helps with protein folding (DNAJB1) and another (protein kinase A) that’s typically involved in cell signaling. In this study, researchers have found that DNAJ-PKAc acts like a scaffold, bringing together other proteins that contribute …