Ambry Genetics Data Enhances BRCA2 Variant Classification for Hereditary Cancers
Ambry Genetics, a leader in clinical genomic testing, has announced its contribution to a groundbreaking study published in Nature, which significantly enhances the understanding of BRCA2 gene variants. As genetic testing becomes increasingly common, the challenge of interpreting the vast number of detected variants has become critical. This study utilized CRISPR/Cas9 gene editing technology to functionally characterize nearly 7,000 BRCA2 variants. The goal was to help resolve variants of uncertain significance (VUS) and improve clinical decision-making for patients with hereditary BRCA2-linked cancers.
BRCA2 is a well-established and clinically significant gene known for its role in cancer predisposition. Pathogenic variants in BRCA2 are associated with an increased risk of several cancers, including those of the breast, ovary, prostate, and pancreas. Over the years, BRCA2 testing has become a cornerstone of hereditary cancer testing. However, despite the gene’s clinical importance, over 5,000 BRCA2 variants are classified as variants of uncertain significance (VUS) in the National Institute of Health’s (NIH) ClinVar database. These variants are often categorized as VUS due to a lack of sufficient evidence to determine their clinical significance.
In a groundbreaking study, an interdisciplinary team of researchers, including experts from Mayo Clinic, H. Lee Moffitt Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Hospital Clinico San Carlos, Memorial Sloan Kettering Cancer Center, Duke University, and Ambry Genetics, worked together to address this issue. The study aimed to evaluate the functional impact of these BRCA2 variants on cancer development, thereby helping to resolve the uncertainty surrounding their classification.
The team’s research utilized functional genetic data to assess nearly 7,000 BRCA2 variants. By integrating this data with clinical analysis, the researchers were able to make significant strides in understanding the role of these variants in cancer pathogenesis. The study’s findings were incorporated into a ClinGen/ACMG/AMP model, which is widely used for clinical interpretation of genetic variants. This integration resulted in a remarkable 91% classification rate, showcasing the potential for improving hereditary cancer testing across all test providers.
Marcy Richardson, PhD, Associate Director of Clinical Research at Ambry Genetics, emphasized the importance of these findings, stating, “These results illustrate the power of combining functional genetic data with clinical analysis to enhance our understanding of hereditary cancer risk and optimize clinical management.” By utilizing functional testing of cancer-associated genes, the clinical community can now offer patients more accurate, data-driven recommendations for managing their cancer risk.
Fergus J. Couch, Ph.D., Professor at Mayo Clinic and lead author of the study, highlighted the collaborative nature of the research, saying, “These findings demonstrate the value of collaborative research in advancing our understanding of BRCA2 variants, improving classification methods that support more accurate risk assessments and informed clinical care.” The integration of functional studies with clinical data enables clinicians to better assess cancer risks, providing valuable tools to guide patient management.
Elizabeth Chao, MD, FACMG, Chief Medical Officer at Ambry Genetics, stressed the broader significance of genetic testing and variant analysis in modern medicine. “Genetic testing and variant analysis are paving the way towards truly personalized clinical care for patients before they have cancer,” Chao noted. “This research moves us beyond the era when clinical decisions were primarily based on family history, which often left clinicians and patients feeling powerless to intervene before cancer onset.” The improved classification of genetic variants across diverse populations will help clinicians make more informed decisions regarding cancer prevention and management.
This study was co-published alongside another related research paper conducted by the NIH, which used a different model to examine similar issues. Together, these studies represent a major step forward in the classification of genetic variants and provide critical data that will help clinicians better assess cancer risks tied to genetic mutations. These efforts are expected to lead to more accurate genetic tests, ensuring that patients with hereditary cancer risks receive the most appropriate care.
Ambry Genetics is at the forefront of transforming scientific research into clinically actionable results. The company has a long history of leveraging its deep understanding of the human genome to create innovative genetic tests that improve health outcomes. With over 25 years of experience and a growing database developed in collaboration with academic, corporate, and pharmaceutical partners, Ambry Genetics continues to lead the way in genetic testing. Its work enables clinicians to confidently guide patient health decisions, particularly in the context of hereditary cancer risk.
About Ambry Genetics
Ambry Genetics is a leading provider of genetic testing, specializing in translating scientific research into clinically actionable results. The company is dedicated to improving health by deepening our understanding of the relationship between genetics and disease. Ambry’s innovative products and comprehensive analysis empower clinicians to make confident decisions about patient care. With a strong track record of discoveries over the past 25 years, Ambry Genetics continues to expand its database in collaboration with academic, corporate, and pharmaceutical partners. As a result, the company is often the first to market with new products that help clinicians improve patient health outcomes.
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