癌性和非癌性组织中的突变谱和突变特征可以通过各种已建立的大规模并行测序（或下一代测序）技术来识别，包括全外显子组或全基因组测序，以及最近的纠错/双工测序。一个尚未充分探索的领域是对作为诱变暴露标记的突变特征进行基因组规模分析，及其对应用于福尔马林固定或酒精固定石蜡包埋的存档生物样本的癌症驱动事件的影响。这篇综述展示了下一代测序方法在固定存档组织中的成功应用，包括对特定组织固定相关 DNA 损伤的描述，这些损伤表现为人为特征，与生物诱变过程产生的真实特征不同。总的来说，我们讨论并展示了应用于固定存档生物样本的下一代测序技术如何增强我们对癌症原因的理解，包括外源性癌症风险因子的诱变效应，以及旨在减少可避免的致癌暴露的预防工作的影响。版权所有 © 2024 年。由 Elsevier B.V 出版。

Mutation spectra and mutational signatures in cancerous and non-cancerous tissues can be identified by various established techniques of massively parallel sequencing (or next-generation sequencing) including whole-exome or whole-genome sequencing, and more recently by error-corrected/duplex sequencing. One rather underexplored area has been the genome-scale analysis of mutational signatures as markers of mutagenic exposures, and their impact on cancer driver events applied to formalin-fixed or alcohol-fixed paraffin embedded archived biospecimens. This review showcases successful application of the next-generation sequencing methodologies in fixed archived tissues, including the delineation of the specific tissue fixation-related DNA damage manifesting as artifactual signatures, distinguishable from the true signatures that arise from biological mutagenic processes. Overall, we discuss and demonstrate how next-generation sequencing techniques applied to fixed archived biospecimens can enhance our understanding of cancer causes including mutagenic effects of extrinsic cancer risk agents, and the implications for prevention efforts aimed at reducing avoidable cancer-causing exposures.Copyright © 2024. Published by Elsevier B.V.