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Ambry’s Contributions to MAVEs Support Thousands of Patient Reclassifications and Expand to New Genes
New study published in Nature Communications builds on Ambry’s contributions to MAVE research to deepen understanding of PALB2 and its role in hereditary
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[{"type":"text","content":"\nNew study published in Nature Communications builds on Ambry’s contributions to MAVE research to deepen understanding of PALB2 and its role in hereditary cancer predisposition.\n\n\n ALISO VIEJO, Calif.--(BUSINESS WIRE)--\nAmbry Genetics, a leader in clinical genomic testing, and now a wholly owned subsidiary of Tempus AI, Inc. (NASDAQ: TEM), today announced its contribution to new research leveraging Multiplexed Assays of Variant Effect (MAVEs) studies to advance interpretation of hereditary cancer-linked genetic variants, published in Nature Communications. Led by researchers at Leiden University Medical Center in the Netherlands and supported by Ambry’s extensive clinical data, this study revealed previously unfounded missense pathogenicity in PALB2.\n\n\nPALB2 is one of the most clinically important genes associated with hereditary breast and pancreatic cancer. However, many PALB2 missense variants have remained difficult to interpret due to limited evidence and lack of support for missense variation as a mechanism of disease. This newly published study helps address these challenges by using MAVEs — ultra-high-throughput functional screens that evaluate thousands of variants— to reveal how variants influence clinically relevant functions.\n\n\nResearchers assayed 84% of all possible missense variants across 11 PALB2 exons, generating functional data for 6,718 variants. The results reflected 3,904 variants as functionally normal (58%), 2,422 as intermediate (36%), and 392 as functionally abnormal (6%) based on PARP inhibitor sensitivity, a measure of homologous recombination. These findings pave the way for improved variant interpretation, clinical management, and personalized treatment strategies for individuals carrying PALB2 variants.\n\n\n“This study represents a major step forward in our ability to interpret PALB2 variants at scale,” said Steven M. Lipkin, MD, PhD, FACMG, Chief Medical Officer at Ambry Genetics. “MAVEs are generating the type of functional evidence that will help bridge the gap between genomic data and clinical decision-making. This research is a crucial part of our broader mission to advance precision medicine, reduce the rate of variants of uncertain significance, and improve outcomes for individuals at risk for hereditary cancer.”\n\n\nThe PALB2 findings build on Ambry’s earlier contributions to MA...