Advances of the Low-Error Next-Generation Sequencing Technology Applied in Cancer Research and Drug Mutagenic Risk Evaluation
Objective:To explore the advances of low-error next-generation sequencing(NGS)technology in cancer research and drug mutagenicity evaluation.Methods:The technical progress,advantages and disadvantages of low-error NGS and its application in cancer research and drug mutagenicity/carcinogenicity evaluation were summarized by reviewing literatures and collecting data in recent years.Results:The background error 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 tumor monitoring and drug regulation.In addition,the minimum error rate of ecNGS technologies such as HiFi-Seq and PECC-Seq can be reduced to 10-8,which can detect ultra-low frequency mutations in cell/tissue caused by short-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 has not been popularized in clinical,toxicology and risk assessment fields.However,these can directly detect drug-induced tissue/cell mutations and obtain the specific mutation spectrum of drugs,which can be an alternative or supplement method of the existing mutagenicity tests,incorporate relevant guidelines,and become the gold standard for early drug genetic toxicity and carcinogenicity screening.
next-generation sequencing technologymutagenicitycarcinogenicitycancer researchultra-low frequency sequencingdrug regulation
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