容错校正的下一代测序（ecNGS）迅速崛起为一种宝贵、高度敏感和准确的方法，用于检测和表征DNA可分离的任何细胞类型、组织或生物体中的突变。最近的致突变性和致癌性研究已经使用ecNGS来量化药物/化学物质诱导的突变和与癌症风险相关的突变谱。ecNGS在遗传毒性评估中具有潜在应用，作为传统模型的新读出方法，用于三维器官培养的突变研究，以及用于检测基因编辑工具的非靶效应。此外，早期数据表明，ecNGS可以作为机制不可知的早期癌症潜在标志物测量突变的克隆扩张，并且可以直接评估人类生物监测研究中的突变负荷。在本综述中，我们讨论了有前途的应用、挑战、限制和需要推动ecNGS的监管测试和采用的关键数据倡议，包括推动安全评估、增加突变性和致癌性机制的证据链、识别早期癌症风险生物标志物，以及管理化学物暴露对人类健康风险的影响。 版权所有©2023作者。由Elsevier B.V.出版。保留所有权利。

Error-corrected Next Generation Sequencing (ecNGS) is rapidly emerging as a valuable, highly sensitive and accurate method for detecting and characterising 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.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.