基因组规模的突变签名分析在存档固定组织中
Genome-scale mutational signature analysis in archived fixed tissues
影响因子:4.20000
分区:医学2区 / 生物工程与应用微生物2区 遗传学2区 毒理学2区
发表日期:2024
作者:
Bérénice Chavanel, François Virard, Vincent Cahais, Claire Renard, Cécilia Sirand, Kim M Smits, Leo J Schouten, Béatrice Fervers, Barbara Charbotel, Behnoush Abedi-Ardekani, Michael Korenjak, Jiri Zavadil
摘要
可以通过各种大规模平行测序（或下一代测序）（包括全异位或全基因组测序）以及最近通过错误校正/二线测序的各种既定的技术（或下一代测序）来鉴定癌症和非癌组织中的突变谱和突变特征。一个相当不受欢迎的区域是将突变特征作为诱变暴露的标志物的基因组规模分析，以及它们对应用于福尔马林固定或酒精固定的石蜡嵌入的存档生物测量的癌症驱动因素的影响。这篇综述展示了下一代测序方法在存档固定组织中的成功应用，包括描述特定组织固定相关的DNA损伤，表现为人为签名，可与生物诱变过程产生的真实特征区分开。总体而言，我们讨论并展示了如何将下一代测序技术应用于存档的固定生物测量，可以增强我们对癌症原因的理解，包括外在癌症风险剂的诱变作用，以及旨在减少可避免的癌症造成暴露的预防工作的影响。
Abstract
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 applications of the next-generation sequencing methodologies in archived fixed 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 archived fixed 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.