2023-05-12 07:30:20
Research into rare cancers can be complicated because there are few patients and therefore little tumor material is available. So is fibrolamellar carcinoma (FLC), a rare type of liver cancer that mainly affects teens and young adults. The aggressive tumor occurs in about one in five million people each year and there is no treatment for it.
We still don’t know much about this rare cancer. “The best way to study rare tumors is in human mini-organs, so-called organoids,” says Delilah Hendriks, researcher at the Hubrecht Institute. In 2018, scientists there developed the first miniature livers. Just like the real thing, but not quite – the clumps of cells behave like cells in our body, but only the main cell type of the liver, the hepatocyte, is present. In the top image, different colors show the three-dimensional structure of the organoids.
Scientists from the Princess Máxima Center and the Hubrecht Institute investigated the effect of various mutations on tumor growth in the mini-livers. Using crispr-cas9, a molecular tool for modifying DNA, they mutated several genes in healthy organoids. For one of those genes, the PKA gene, it was already known that a fusion with another gene leads to FLC. Now, for the first time, the scientists could see this tumor developing in the mini-livers. They published their results Nature Communications.
“It was previously assumed that a mutation in this gene was always the cause of FLC, but a recent study suggested other candidates,” says Benedetta Artegiani, who co-supervised the study from PMC. Knocking out these two candidates produced a completely different picture: where the tumors with the PKA fusion developed quiescently, the tumors with the other mutations grew exponentially.
This is clearly visible in the large image above. Each cluster of luminous dots is an organoid, in which cell nuclei are colored blue. Transformed hepatocytes are red and cancer proteins are green. Different organoids are colored differently due to showing different degrees of tumor formation.
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