Summary of Not Just One Type – Identifying Cancer Genes’ Multiple Personalities:
Researchers at Cold Spring Harbor Laboratory have developed a new method for modeling specific subtypes of liver cancer tumors using the gene-editing tool CRISPR-Cas9. The device generated different cancer-causing gain-of-function mutations in mice, resulting in two distinct tumor subtypes with varying characteristics. The study identified isoforms, highly similar proteins produced from the same gene, as the key to generating these different tumor subtypes. This new method could help researchers develop therapeutic interventions for cancer and other diseases.
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CRISPR Gene-Editing Tool Used to Create Liver Cancer Subtypes in Mice
Liver cancer is one of the most deadly malignancies, and it can be challenging to treat because various subtypes of the disease can develop from the same genetic mutation. However, a Cold Spring Harbor Laboratory research team has discovered a new technique to create multiple subtypes of liver cancer tumors using the CRISPR-Cas9 gene-editing tool.
The CRISPR-Cas9 Tool
CRISPR-Cas9 gene editing is a revolutionary tool that allows researchers to make precise and targeted changes to DNA sequences. It delivers a modified RNA molecule to cells, recognizing and binding to specific DNA sequences. Once the guide RNA has been attached, the Cas9 nuclease enzyme will cut the DNA strand, enabling researchers to substitute or delete genes.
How Gene Mutation Causes Liver Cancer
The human body requires genes to create proteins that fulfill various essential functions. Highly similar proteins produced from the same gene are called isoforms. The process of exon skipping — where different parts of a gene are spliced together — can generate these isoforms.
Different isoforms create different tumors, and various cancer subtypes are associated. Exon skipping is a potential therapeutic approach for treating cancer and other diseases.
Creating Liver Cancer Subtypes in Mice
The researchers produced two distinct tumor subtypes by targeting a single section of the mouse gene, Ctnnb1, with CRISPR. This cancer-causing gain-of-function mutation enhances protein activity to promote tumor growth.
The team could identify which isoform was linked to each subtype by sequencing the tumors. The mutations targeted by the researchers can lead to colon and liver cancers.
The First Use of CRISPR to Create Different Cancer-Causing Mutations in Mice
This is the first time CRISPR has been used to generate different cancer-causing gain-of-function mutations in mice, and it is also the first successful attempt to create two other liver cancer subtypes in living cells.
Implications for Cancer Treatment
Targeting exon skipping has become a potential therapeutic approach for treating cancer and other diseases. By using CRISPR to model subtypes of liver cancer tumors and discovering the isoforms associated with these different subtypes, the researchers hope to find new therapeutic interventions to treat cancer.
Ultimately, the researchers want to find the best models to study cancer biology and find a way to cure cancer. The study was funded by the Oliver S. and Jennie R. Donaldson Charitable Trust, the National Institutes of Health, the National Cancer Institute, the STARR Cancer Consortium, the Swedish Research Council, the Mark Foundation For Cancer Research, and the National Center for Advancing Translational Sciences (NCATS).
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