Scholarlink

<p>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 <i>RAD51D</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

HR eye & MMR eye: one-day assessment of DNA repair-defective tumors eligible for targeted therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月12日

查看全文
  • Shinta Saito,
  • Shingo Kato,
  • Usaki Arai,
  • Atsuki En,
  • Jun Tsunezumi,
  • Taichi Mizushima,
  • Kensuke Tateishi,
  • Noritaka Adachi

摘要

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.