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journal publication
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 …
Fibrolamellar carcinoma (FLC) is driven by a unique fusion protein called DNAJB1::PRKACA (DP). This fusion is responsible for the growth of the tumor cells, and without it, the tumor dies. Unfortunately, targeting this fusion with drugs has proven extremely difficult, because the fusion’s active site is almost identical to that of normal protein kinase A …
This paper was written by a large team of researchers at the University of Washington, Fred Hutchinson Cancer Center, and Cornell University, led by senior authors Dr. Venu G. Pillarisetty and Dr. Praveen Sethupathy. The group includes surgeons, cancer biologists, immunologists, and data scientists who focus on fibrolamellar carcinoma (FLC). The goal of the study …
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 …
This study represents one of the most comprehensive molecular analyses performed on fibrolamellar carcinoma (FLC). Using more than 1,400 tumor and normal liver samples, including 220 FLC and FLC‑like tumors, the research team used techniques including RNA sequencing, DNA sequencing, proteomics, methylation analysis, and spatial single‑cell mapping to better understand FLC at the molecular level. …
The European Association for the Study of the Liver (EASL) convened an international, multidisciplinary panel to evaluate and summarize current knowledge on rare primary liver cancers. The resulting paper focused in three major rare liver cancers, combined hepatocellular–cholangiocarcinoma (cHCC‑CCA), fibrolamellar carcinoma (FLC), and hepatic epithelioid hemangioendothelioma (HEHE), as well as several ultra‑rare varieties. Due to …
Fibrolamellar carcinoma (FLC) is a rare, aggressive liver cancer affecting adolescents and young adults. Nearly all cases contain the same genetic abnormality — a fusion protein called DNAJ‑PKAc. This study provides clear evidence that the fusion protein fundamentally reshapes both the metabolism of the cancer and immune behavior. Importantly, this rewiring reveals a specific therapeutic …
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 …
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 …