Mutations in our genes can lead to severe health problems like colon or liver cancer. The complexity of cancer is such that mutations in the same genes can lead to different subtypes of tumors in different individuals. Currently, scientists lack a reliable method to produce these tumor subtypes for study in the lab. However, Cold Spring Harbor Laboratory Assistant Professor Semir Beyaz has created a new technique using the gene-editing tool CRISPR-Cas9 to model certain liver cancer tumor subtypes.
Understanding Genes and Isoforms
Genes carry information that our bodies use to create proteins. Proteins produced from highly similar genes are known as isoforms, and they generate different tumors. This process, known as exon skipping, involves stitching together multiple parts of a gene to form a new version of a protein. Beyaz explains that different isoforms can cause different cancer subtypes with varying characteristics.
Generating Different Tumor Subtypes with CRISPR-Cas9
Beyaz and his colleagues produced two distinct liver tumor subtypes in mice by targeting a single section of the gene Ctnnb1 using CRISPR-Cas9. While the tool is primarily used to inhibit gene function, this was the first time it had been used to generate different cancer-causing gain-of-function mutations in mice. These mutations enhance protein activity and promote tumor growth. The team then sequenced each tumor subtype to determine the isoform associated with the observed differences.
Confirming Isoform-Caused Variances
To confirm that the isoforms were indeed causing the variances, the researchers produced them in mice without using CRISPR-Cas9. They discovered that they could generate the two different tumor subtypes with their respective characteristics. Additionally, both of these liver tumor subtypes are found in humans.
Implications for Cancer Treatment
The mutations targeted by Beyaz can lead to colon and liver cancers. Targeting exon skipping has emerged as a potential therapeutic approach for treating cancer and other diseases. Beyaz’s new study method allows researchers to investigate this phenomenon in living mouse cells using CRISPR-Cas9. This platform could eventually help researchers develop new therapeutic interventions. Ultimately, Beyaz explains that the goal is to find the best models to study the biology of cancer and eventually find a cure.
In summary, Beyaz’s new method using CRISPR-Cas9 to model certain liver cancer tumor subtypes has shown great promise in understanding the complexity of cancer. By targeting a single section of a gene, researchers were able to generate different cancer-causing gain-of-function mutations in mice and study the isoforms associated with the observed differences. By confirming that these isoforms caused the variances, this technique may eventually lead to new therapeutic interventions for cancer and other diseases.