An up-close look at a mouse’s liver; the cells with dark centers were turned cancerous using a new gene-editing strategy devised by Semir Beyaz’s lab. Credit: Beyaz lab/Cold Spring Harbor Laboratory
Key points:
- A new method can model certain liver cancer tumor subtypes using CRISPR-Cas9.
- Researchers were able to produce two distinct tumor subtypes by targeting a single section of the mouse gene.
- Investigating gene mutations in mice cells could someday help researchers develop new therapeutic interventions.
Gene mutations can lead to a host of health problems, including colon and liver cancer. Cancer remains a mystery in many ways since there can be mutations in the same genes, leading to different subtypes of tumors in people. Unfortunately, scientists still lack a good way to produce tumor subtypes for study in the lab.
In a paper published in Pathological Studies, Cold Spring Harbor Laboratory Assistant Professor Semir Beyaz shares a new method that can model certain liver cancer tumor subtypes using the gene-editing tool CRISPR-Cas9.
Our bodies need genes because they carry information needed to create proteins. Isoforms are highly similar proteins produced from the same gene. Different isoforms generate different tumors. When multiple parts of a gene are stitched together to make a different version of a protein its called exon skipping.
“Everyone thinks that cancer is just one type, but with different isoforms, you can end up with cancer subtypes that have different characteristics,” explains Beyaz.
Beyaz and his colleagues produced two distinct tumor subtypes by targeting a single section of the mouse gene, Ctnnb1, with CRISPR. This is the first time CRISPR has been used to generate different cancer-causing gain-of-function mutations in mice. These mutations enhance protein activity to promote tumor growth. The team sequenced each tumor subtype to determine which isoform was associated with these differences.
They then confirmed these isoforms caused the variances by producing them in the mouse without using CRISPR. The team found they were indeed able to generate the two different tumor subtypes—something that can happen in humans as well. In fact, the mutations Beyaz targeted can lead to colon and liver cancers.
The new method allows researchers to investigate this phenomenon in living mice cells using CRISPR. The platform could someday help researchers develop new therapeutic interventions.
“Ultimately, what we want to do is find the best models to study the biology of cancer so that we can find a cure,” said Beyaz.