Why Are Isoforms Linked to Tumor Subtypes?

Using CRISPR-Cas9, the gene editing tool, researchers have discovered a new approach to demonstrate certain liver cancer tumor subtypes.

What are Isoforms and Their Role in Cancer

Genes contain the information our bodies need to create proteins. Highly similar proteins produced from the same gene are called isoforms. Different isoforms generate different tumors. This process is known as exon skipping, where multiple parts of a gene are stitched together to make a different version of a protein. “Everyone thinks that cancer is just one type,” Beyaz explains. “But with different isoforms, you can end up with cancer subtypes that have different characteristics.”

Beyaz and his colleagues produced two distinct tumor subtypes by targeting a single section of the mouse gene, Ctnnb1, with CRISPR. The tool is mostly used to inhibit gene function. 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 figure out which isoform was associated with the differences they observed.

Next, to confirm that these isoforms actually caused the variances, they produced them in the mouse without using CRISPR. They found that they were indeed able to generate the two different tumor subtypes with their respective characteristics. Both of these liver tumor subtypes are also found in humans.

The mutations Beyaz targeted 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 mice cells using CRISPR. The platform could someday help researchers develop new therapeutic interventions. “Ultimately,” Beyaz explains, “what we want to do is find the best models to study the biology of cancer so that we can find a cure.”

Source-Eurekalert