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HR eye & MMR eye: one-day assessment of DNA repair-defective tumors eligible for targeted therapy
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Journal Article
HR eye & MMR eye: one-day assessment of DNA repair-defective tumors eligible for targeted therapy
2025
Overview
Homologous recombination (HR) and mismatch repair (MMR) act as guardians of the human genome, and defects in HR or MMR are causative in at least a quarter of all malignant tumors. Although these DNA repair-deficient tumors are eligible for effective targeted therapies, fully reliable diagnostic strategies based on functional assay have yet to be established, potentially limiting safe and proper application of the molecular targeted drugs. Here we show that transient transfection of artificial DNA substrates enables ultrarapid detection of HR and MMR. This finding led us to develop a diagnostic strategy that can determine the cellular HR/MMR status within one day without the need for control cells or tissues. Notably, the accuracy of this method allowed the discovery of a pathogenic
RAD51D
mutation, which was missed by existing companion diagnostic tests. Our methods, termed HR eye and MMR eye, are applicable to frozen tumor tissues and roughly predict the response to therapy. Overall, the findings presented here could pave the way for accurately assessing malignant tumors with functional defects in HR or MMR, a step forward in accelerating precision medicine.
DNA repair-deficient tumours are eligible for effective targeted therapies, but reliable diagnostic strategies based on functional assays are needed. Here the authors develop methods for the rapid assessment of homologous recombination and mismatch repair status in tumor tissues, allowing drug efficacy to be predicted.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
