Fibrolamellar hepatocellular carcinoma, a form of liver cancer mainly found among children and young people, currently has surgery as the only treatment available. But even then less than 40 percent of patients will survive beyond five years.
It might help to discover what causes it.
In a study published in Gastroenterology, researchers from the University of Copenhagen using mouse studies have shown that the coupling of the two genes through a mutation causes a cancer tumor to develop in the liver. The researchers have made sure the genetic composition of the mutation in the mice is identical with the mutation found in human patients. This makes the researchers conclude that the gene mutation also leads to cancer in humans.
"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," says the author of the study, Associate Professor Morten Frödin from the Biotech Research&Innovation Centre, BRIC.
The researchers had suspected this mutation to be the cause of cancer, because an American student a couple of years ago sequenced the DNA in her own tumor and the tumor of other patients suffering from this fatal form of liver cancer. She discovered that all the patients suffering from the disease had the same mutation in their DNA.
The researchers have used CRISPR/Cas9 to produce which would provoke precisely the desired fusion of the two genes. The reagents were injected into the mice's tails and then transported via the bloodstream to the liver. In the liver they created a mutation identical with the human mutation previously discovered by the American researcher.
Then the researchers were able to conclude that 12 or the 15 mice developed the expected type of tumor in the liver, while none of the 11 control mice did. According to the researchers, the result contains almost no 'noise', which may otherwise explain the development of cancer.
"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," said co-author Francesco Niola, Assistant Professor from BRIC.