Mutation Models

Fibrolamellar carcinoma (FLC) is an often fatal liver cancer affecting young people. The molecular mechanisms driving it are unclear, partly because of a lack of experimental models. Researchers now create human liver organoids (pictured using fluorescent microscopy) of healthy liver tissue (top, left) and, using genetic engineering technology, CRISPR, those that replicate liver with the different genetic faults found in FLC. Most common is the fusion of genes DNAJB1 and PRKACA (top, right), and also found are faults in PRKAR2A and BAP1 genes separately and together (bottom, left to right). FLC organoids mimicked tumour samples from patients and their liver cells regressed to an immature state. However, only faulty BAP1 and PRKAR2A together caused liver cells to turn into progenitor-like cells that, unlike normal liver cells, could grow in liver ducts. Meanwhile, DNAJB1-PRKACA organoids showed milder cancer features compared with other FLC organoids. Together, these FLC models hold promise for studying FLC progression.

Written by Lux Fatimathas

Lux Fatimathas

Writer

Having pursued science through a career in research, communications and publishing, she is currently a writer and editor for a healthcare marketing agency and also juggles freelance science writing.

• Image from work by Laura Rüland and colleagues
• The Princess Maxima Center for Pediatric Oncology, and the Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht, The Netherlands
• Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)
• Published in Nature Communications, May 2023