Error-corrected Next Generation Sequencing (ecNGS) is rapidly emerging as a valuable, highly sensitive and accurate method for detecting and characterizing mutations in any cell type, tissue or organism from which DNA can be isolated. Recent mutagenicity and carcinogenicity studies have used ecNGS to quantify drug-/chemical-induced mutations and mutational spectra associated with cancer risk. ecNGS has potential applications in genotoxicity assessment as a new readout for traditional models, for mutagenesis studies in 3D organotypic cultures, and for detecting off-target effects of gene editing tools. Additionally, early data suggest that ecNGS can measure clonal expansion of mutations as a mechanism-agnostic early marker of carcinogenic potential and can evaluate mutational load directly in human biomonitoring studies. In this review, we discuss promising applications, challenges, limitations, and key data initiatives needed to enable regulatory testing and adoption of ecNGS – including for advancing safety assessment, augmenting weight-of-evidence for mutagenicity and carcinogenicity mechanisms, identifying early biomarkers of cancer risk, and managing human health risk from chemical exposures.

纠错下一代测序 (ecNGS) 正在迅速成为一种有价值、高度灵敏且准确的方法，用于检测和表征任何可以分离 DNA 的细胞类型、组织或生物体中的突变。最近的致突变性和致癌性研究已使用 ecNGS 来量化药物/化学品诱导的突变以及与癌症风险相关的突变谱。ecNGS 在基因毒性评估、3D 器官型培养中的突变研究以及检测基因编辑工具的脱靶效应方面具有潜在的应用，作为传统模型的新读数。此外，早期数据表明，ecNGS 可以测量突变的克隆扩展，作为致癌潜力的机制不可知的早期标记，并且可以在人类生物监测研究中直接评估突变负荷。在这篇综述中，我们讨论了实现监管测试和采用 ecNGS 所需的有前景的应用、挑战、局限性和关键数据举措，包括推进安全评估、增强致突变性和致癌性机制的证据权重、识别癌症的早期生物标志物风险，并管理化学品暴露造成的人类健康风险。