Arthur says this finding is critical because it is the first time that a mutation has been discovered in the three prime untranslated region (3’-UTR) of a gene. This structure is important in maintaining the stability of the ribonucleic acid (RNA) copy of genes known as messenger RNA.
She explains that cancers are normally caused by mutations in DNA that directly change the gene product (protein).
“So we don’t know that much about mutations in the 3’-UTR. These sections do not make the protein, which is where cancers start, but some of them help to regulate when and how much of the protein is made.”
In this case, the team found that an abundance of the protein from an oncogene known as NFKBIZ, resulting from UTR mutations described here. This, in turn, is thought to activate what is known as the NF-kappaB pathway, a regulatory system in cells that can drive the growth of cancer cells and is thought to make DLBCL more difficult to treat.
The team is intent on learning more about the function of NFKBIZ and how the mutation is involved in cancer.
Arthur says that if the NFKBIZ gene proves to be an important player in DLBCL, it will be useful in helping clinicians decide which drugs will be most effective in treating patients with DLBCL.
“Having a mutation in this gene may make patients more resistant to some drugs, while susceptible to others,” she says.
“This where personalized medicine could come into play. Treating patients based upon mutations specific to their cancer will correspond to better treatment outcomes and give patients the best chance of being cured.”
The study was published in Nature Communications.
Morin is a Michael Smith Foundation for Health Research Scholar. The study was also supported by the Terry Fox Research Institute.