存档固定组织中基因组规模的突变特征分析
Genome-scale mutational signature analysis in archived fixed tissues
DOI 原文链接
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影响因子:4.2
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
DOI:
10.1016/j.mrrev.2024.108512
摘要
癌变组织与非癌组织中的突变谱和突变特征可以通过各种成熟的高通量测序（或下一代测序）技术识别，包括全外显子测序或全基因组测序，以及近年来的错误校正/双链测序。一个相对较少涉及的领域是将突变特征作为突变诱导暴露的标志以及其对癌症驱动事件影响的基因组尺度分析，应用于福尔马林固定或酒精固定的石蜡包埋存档样本。本综述展示了下一代测序技术在存档固定组织中的成功应用，包括明确因组织固定引起的DNA损伤表现为伪影特征，与由生物学突变过程产生的真实特征区分开来。总体而言，我们讨论并展示了将下一代测序技术应用于存档固定生物样本如何增强对癌症成因的理解，包括外源性癌症风险因子的突变作用及其对预防努力减少可避免癌因暴露的意义。
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.