OCT 18, 2017 2:43 PM PDT

The Genetic Cause of Liver Cancer Identified

WRITTEN BY: Xuan Pham

Image credit: Pixabay.com

Using gene-editing technology in mice, scientists implicated a new fusion gene in the development of liver cancer. Because the same genes in humans are already known to be involved in liver cancer, the same gene fusion event presents a new therapeutic target for this disease.

Liver cancer strikes nearly 40,000 adults in the US annually. As the tenth most common cancer types and one of the most difficult-to-treat diseases, early diagnosis is crucial to good outcome for patients.

One form of liver cancer, known as fibrolamellar hepatocellular carcinoma (FL-HCC), primarily affects young and seemingly healthy people. While a mutation that fuses the genes DNAJB1 and PRKACA have been observed in many of these cases, scientists had yet to show how this fusion event led to liver tumor formation.

To better study this gene fusion event, scientists at the University of Copenhagen used CRISPR/Cas9 gene-editing technique to replicate the Dnajb1-Prkaca fusion in mice. In the absence of any other mutation, 80 percent of mice with the Dnajb1-Prkaca fusion gene grew tumors in the liver. By contrast, mice without this mutation had no such tumor formation.

“We are now able to document that this mutation is the cause of this form of cancer. We suspected the mutation, but it is the first time it has been documented that it in fact does cause the disease. This makes it an obvious target for future treatment,” said Morten Frödin, Associate Professor the Biotech Research & Innovation Centre, BRIC, and the study’s senior author.

“The mice we used were "wild mice," in a scientific sense, which in practice means that they were completely normal. In other studies researchers deliberately damage the mice's liver to imitate a liver disease found among human patients or expose them to several different forms of mutations which may cause cancer. This was not necessary here. Because of our genetic design based on CRISPR/Cas9-technology we are certain that the main factor that can explain the cancer is the fusion of the two genes,” explained Francesco Niola, Assistant Professor from BRIC, and the study’s co-author.

The clear genetic indication behind FL-HCC means better, more potent therapeutic targets are possible. Reportedly, the team already has an action plan and is actively working with a large pharmaceutical company for testing and development.

Additional sources: University of Copenhagen

About the Author
Bachelor's (BA/BS/Other)
I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
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