new insights into BRCA2 gene variants

Advancing cancer risk assessment — Credit: Unsplash+.

A groundbreaking study led by the Mayo Clinic Comprehensive Cancer Center has significantly deepened our understanding of genetic alterations in the BRCA2 gene, a major factor in hereditary cancer risk.

This research marks a significant leap forward in the accuracy of genetic testing and personalized healthcare for people carrying variants of this crucial gene.

The study focused on the DNA-binding domain of BRCA2, analyzing nearly 7,000 possible genetic variants using CRISPR-Cas9, a cutting-edge gene-editing technology.

By evaluating how these variants affect the gene’s function, researchers successfully classified 91% of previously uncertain variants, known as variants of uncertain significance (VUS).

This means that health care providers can now offer much clearer guidance about cancer risk and tailor prevention and treatment strategies more effectively.

Why Is BRCA2 Important?

The BRCA2 gene plays a vital role in repairing DNA damage. When mutations occur in this gene, the body’s ability to fix damaged DNA is compromised, increasing the risk of developing cancers such as breast, ovarian, prostate, and pancreatic cancer.

Genetic testing for BRCA2 mutations has become a cornerstone of cancer risk assessment, but many people receiving these tests face uncertainty if their results fall into the VUS category. These are genetic changes whose impact on cancer risk has been unclear—until now.

Key Findings from the Study

The study classified almost 7,000 variants, definitively identifying which ones increase cancer risk and which do not. This vast catalog of classified variants offers several practical benefits:

Reduced Uncertainty for Patients: Many individuals with a VUS worry about their cancer risk without clear guidance. This research helps provide definitive answers, reducing anxiety and enabling informed decisions about cancer prevention and treatment.
Personalized Risk Assessments: With 91% of VUS in the BRCA2 DNA-binding domain now classified, healthcare providers can give more precise cancer risk assessments. For patients, this means personalized screening and preventive measures.
Improved Treatment Options: The findings will help identify patients with breast, ovarian, pancreatic, or prostate cancer who might benefit from targeted therapies like PARP inhibitors. These drugs are designed to exploit the weaknesses in cancer cells caused by BRCA2 mutations, offering more effective treatment.
Direct Impact on Genetic Testing Labs: Laboratories and expert panels, like the ClinVar BRCA1/2 panel, can now incorporate this data into genetic testing reports, ensuring patients receive up-to-date and accurate information.

A Foundation for Future Research

Dr. Fergus Couch, a lead researcher on the study, highlighted the importance of this achievement, stating, “We now have a catalog of every possible VUS in this part of BRCA2 that can be used to guide clinical care.”

While this study focuses on a specific region of the BRCA2 gene, it sets the stage for future research to classify all variants across the entire gene and across diverse populations.

This progress not only benefits individuals currently undergoing genetic testing but also broadens the potential for risk assessments for various cancer types. By expanding knowledge about BRCA2 mutations, scientists can improve cancer care and prevention strategies worldwide.

A Path Toward Precision Medicine

This study represents a major advancement in understanding how genetic variants contribute to cancer risk. By addressing the uncertainty surrounding BRCA2 VUS, the findings pave the way for more accurate and personalized healthcare.

Whether it’s helping patients make informed decisions about cancer prevention or guiding treatment for those already affected, this research has immediate and far-reaching implications. With the foundation now laid, the future of cancer genetics looks even more promising.

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The research findings can be found in Nature.