人体中每个细胞的基因组不断受到大量的外源和内源过程的攻击,这些过程可能会破坏DNA。如果未成功修复,DNA损伤通常会永久印记在细胞中,和他们所有的后代,作为体细胞突变。在大多数情况下,这些体细胞突变的模式包含已印记的诱变过程的迹象,称为突变特征。最近的泛癌症基因组分析已经阐明了所有类型的小突变事件的突变特征汇编。包括(1)单碱基取代,(2)双碱基取代,和(3)小的插入/缺失。与小的突变事件相反,where,在大多数情况下,DNA损伤是先决条件,非整倍体,指细胞中染色体的异常数量,通常是DNA复制过程中的错误。这些错误包括DNA复制压力,由错误的微管动力学引起的有丝分裂错误,或内聚缺陷,导致染色体断裂,并可能导致拷贝数(CN)改变(CNA)甚至结构重排。这些畸变还留下基因组疤痕,其可以从测序推断为CN签名和重排签名。小突变事件的突变特征的分析已经得到了广泛的审查,所以我们不会在这里全面地重新审视它们。相反,我们的重点将是总结CNA突变签名的现有知识。由于研究CN签名是一个新兴领域,我们简要总结了小突变事件的突变签名在基础科学中提供的效用,癌症治疗,和癌症预防,我们强调CN签名在每个领域中可能发挥的未来作用。©2022作者由JohnWiley&SonsLtd代表英国和爱尔兰病理学会出版的病理学杂志。
The genome of each cell in the human body is constantly under assault from a plethora of exogenous and endogenous processes that can damage DNA. If not successfully repaired, DNA damage generally becomes permanently imprinted in cells, and all their progenies, as somatic mutations. In most cases, the patterns of these somatic mutations contain the tell-tale signs of the mutagenic processes that have imprinted and are termed mutational signatures. Recent pan-cancer genomic analyses have elucidated the compendium of mutational signatures for all types of small mutational events, including (1) single base substitutions, (2) doublet base substitutions, and (3) small insertions/deletions. In contrast to small mutational events, where, in most cases, DNA damage is a prerequisite, aneuploidy, which refers to the abnormal number of chromosomes in a cell, usually develops from mistakes during DNA replication. Such mistakes include DNA replication stress, mitotic errors caused by faulty microtubule dynamics, or cohesion defects that contribute to chromosomal breakage and can lead to copy number (CN) alterations (CNAs) or even to structural rearrangements. These aberrations also leave behind genomic scars which can be inferred from sequencing as CN signatures and rearrangement signatures. The analyses of mutational signatures of small mutational events have been extensively reviewed, so we will not comprehensively re-examine them here. Rather, our focus will be on summarising the existing knowledge for mutational signatures of CNAs. As studying CN signatures is an emerging field, we briefly summarise the utility that mutational signatures of small mutational events have provided in basic science, cancer treatment, and cancer prevention, and we emphasise the future role that CN signatures may play in each of these fields. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.