Researchers Reclassify Hundreds of BRCA2 Variants Linked to Cancer

In a study published in the journal Nature, researchers reclassified thousands of BRCA2 variants of unknown significance (VUS) as either increasing cancer risk or not. 

If you’ve received BRCA2 genetic testing and don’t have a BRCA2 VUS, these new findings don’t affect you. But if you’ve received a BRCA2 VUS result, it may be worth reaching out to your genetic counselor or the clinic where you had testing done to find out what these findings might mean for you. 

Genetic testing can help you find out if you have genetic changes, or mutations, that increase your risk of developing breast cancer. But sometimes these tests uncover mutations that researchers don’t know enough about to say whether or not they increase the risk of breast or other cancers. These murky mutations are called variants of unknown significance.  

Being told you have a VUS may leave you feeling confused or concerned with the results. Scientists are working to classify these mutations using different technologies. 

The researchers at Mayo Clinic Comprehensive Cancer Center studied the role of almost 7,000 of BRCA2 variants. To do that, they evaluated how VUS from a certain region of the BRCA2 gene impacted human cells.  If a human cell died, that indicated to the researchers that the mutation was harmful (pathogenic).

The majority of mutations (80%) were classified as benign (not cancerous) or likely benign, while 11% were classified as pathogenic (cancerous) or likely pathogenic. The remaining mutations are still classified as VUS. 

“Until now, patients who carried VUS often worried if they would develop cancer, but now with the classification of these variants, we can provide a clearer picture of cancer risk and tailor both prevention strategies as well as breast cancer treatment accordingly,” said study author Fergus Couch, Ph.D., a Zbigniew and Anna M. Scheller professor of medical research at Mayo Clinic, in a press release.

The results of this study are being reviewed by an expert panel that evaluates new BRCA1/2 gene mutation results. Their conclusions may guide genetic testing centers and healthcare professionals on updating test reports.

People with a BRCA2 VUS may be notified about any updates to their VUS results following the review by the expert panel. If you’ve received a BRCA2 VUS result, it may be worth discussing these new findings with your genetic counselor.