| 寇小旋,耿兴超,文海若.低误差第二代测序技术应用于肿瘤研究和药物致突变性风险评价的进展[J].中国药事,2024,38(7):831-838 |
| 低误差第二代测序技术应用于肿瘤研究和药物致突变性风险评价的进展 |
| Advances of the Low-Error Next-Generation Sequencing Technology Applied inCancer Research and Drug Mutagenic Risk Evaluation |
| 投稿时间：2024-03-05 |
| DOI：10.16153/j.1002-7777.2024.07.013 |
| 中文关键词: 第二代测序技术 致突变性 致癌性 肿瘤研究 超低频测序 药品监管 |
| 英文关键词: next-generation sequencing technology mutagenicity carcinogenicity cancer research ultra-lowfrequency sequencing drug regulation |
| 基金项目:药品监管科学全国重点实验室课题“药品杂质遗传毒性评价新技术和生物标志物研究”（编号 2023SKLDRS0128） |
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| 中文摘要: |
| 目的：探讨低误差第二代测序（next-generation sequencing，NGS）技术在肿瘤研究和药物致突变性评价领域的进展。方法：通过查阅文献、收集资料等方法，汇总近年来低误差NGS技术进展、优缺点以及在肿瘤研究和药物致突变性/致癌性评价的应用。结果：传统的NGS技术的背景误差率较高，限制其在低频率突变检测方面的应用。近年开发的多种低误差NGS技术（即校正测序错误的NGS，errorcorrectednext-generation sequencing，ecNGS）可将NGS的检测误差率降低至10-7~10-4或甚至更低，满足肿瘤临床监测和指导用药的需求。此外，HiFi-Seq和PECC-Seq等技术的最低误差率可降低至10-8，可检出药物短期暴露导致的细胞/组织的超低频突变，有助于在药物研发早期评估其致癌性风险。结论：ecNGS技术目前处于开发阶段，尚未标准化，且未在临床、毒理学、风险评估领域推广应用。然而，该方法可直接检出肿瘤早期病变组织中的突变和药物诱导的组织/细胞突变，有望取代或补充现有的致突变性试验方法，纳入相关指导原则，成为药物早期遗传毒性、致癌性筛查的金标准。 |
| 英文摘要: |
| Objective: To explore the advances of low-error next-generation sequencing (NGS) technologyin cancer research and drug mutagenicity evaluation. Methods: The technical progress, advantages anddisadvantages of low-error NGS and its application in cancer research and drug mutagenicity/carcinogenicityevaluation were summarized by reviewing literatures and collecting data in recent years. Results: The backgrounderror rate of traditional NGS technique is high, which limits its application in low frequency mutation detection.Several low-error NGS technologies developed in recent years (i.e., error-corrected next generation sequencing,ecNGS) can reduce the error rate of NGS to 10-7 to 10-4 or even lower, meeting the needs of clinical tumormonitoring and drug regulation. In addition, the minimum error rate of ecNGS technologies such as HiFi-Seqand PECC-Seq can be reduced to 10-8, which can detect ultra-low frequency mutations in cell/tissue caused byshort-term exposure to drugs, helping to assess their carcinogenicity risk in the early stage of drug development.Conclusion: The ecNGS technology is currently in the development stage, it has not been standardized, and hasnot been popularized in clinical, toxicology and risk assessment fi elds. However, these can directly detect druginducedtissue/cell mutations and obtain the specific mutation spectrum of drugs, which can be an alternativeor supplement method of the existing mutagenicity tests, incorporate relevant guidelines, and become the goldstandard for early drug genetic toxicity and carcinogenicity screening. |
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