Dutch scientists at the Princess Máxima Center for pediatric oncology have made significant strides in understanding fibrolamellar carcinoma (FLC), a rare childhood liver cancer affecting mostly adolescents and young adults. By utilizing organoid models and CRISPR-Cas9 gene-editing techniques, the researchers explored how different genetic mutations influence the aggressiveness of tumors, identifying hepatocytes as the probable cell-of-origin for FLC.
Their study, published in Nature Communications, highlights that while mutations in the PKA genes are crucial in tumor formation, they may not suffice alone; the presence of additional mutations, particularly in genes like BAP1 and PRKAR2A, significantly increased tumor aggressiveness. Notably, the research revealed that these mutations might induce a process called transdifferentiation, where healthy hepatocytes transform into ductal cells, further complicating the identification of cancer origins.
These findings not only enhance the current understanding of FLC but may also pave the way for novel therapies and a deeper insight into tumor behavior across patients. The research underscores the necessity for precise genetic targeting in future treatment strategies for this rare form of liver cancer.
