Scientific Publications and Presentations

CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates that the DNAJB1-PRKACA Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma

December 1, 2017

Engelholm, Riaz, ... & Frödin
Journal article published in Gastroenterology

The DNAJB1-PRKACA fusion gene is found in almost all FLC tumors. In order to determine if this gene fusion is a cause of the tumors, these researchers used a CRISPR-Cas9 technique to create a chimeric DNAJB1-PRKACA fusion gene in the livers of otherwise healthy mice. Using the CRISPR-Cas9 system, the researchers created guide RNAs that directed a DNA-cleaving protein called Cas9 to the DNAJB1 and PRKACA gene sequences in the DNA.  There, Cas9 functioned as a “genetic scissors,” cutting the DNA at those particular points, causing them to fuse and create the DNAJB1-PRKACA chimeric gene. Fourteen months after injecting the guide RNAs in mice, the mouse livers were examined for changes. At that time, 80% of the mice had developed liver tumors. In examining those tumors, it was determined that the mouse liver tumors’ appearance and immunohistological characteristics were similar to human FLC, and that the DNAJB1-PRKACA fusion gene was present in the tumor cells.

Implications: These researchers demonstrated that the DNAJB1-PRKACA gene fusion appears to cause the formation of FLC-like tumors in mice and that this fusion is potentially the only change necessary to cause the development of FLC.

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