Non-clonal interphase markers of chromosomal instability in malignancy acquisition and cancer progression

IF 2.4 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2026-07-01 Epub Date: 2026-07-13 DOI:10.1016/j.mrfmmm.2026.111944

Vinícius Bernardo de Oliveira, João Marcos Oliveira-Silva, Giovanna De Souza Maciel, Marcos Samuel Souza Paulino, Laís Bernardo Lopes, Larissa Pereira Damasceno, Maria Eduarda do Vale Uliniki Teixeira, Angel Mauricio Castro-Gamero

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引用次数: 0

Abstract

Chromosomal instability (CIN) is a pervasive feature of cancer and a major driver of tumor heterogeneity, evolution, and therapeutic resistance. Arising predominantly from defects in chromosome segregation, DNA repair, and mitotic fidelity, CIN promotes continuous genomic diversification within tumor cell populations, enabling adaptive responses to intrinsic and extrinsic selective pressures. While clonal chromosomal alterations reflect stabilized genomic configurations selected during tumor evolution, non-clonal interphase markers of chromosomal instability represent transient, low-frequency events that capture ongoing microevolutionary dynamics and genomic plasticity. This review provides a comprehensive synthesis of current knowledge regarding both classical and non-classical markers of CIN evaluated during interphase, including micronuclei, nucleoplasmic bridges, nuclear buds, cytoplasmic chromatin, massive chromosomal segregation errors, chromosomal fragmentation, and genomic chaos-related phenomena. We discuss the cellular mechanisms underlying their formation, their contribution to structural and numerical chromosomal alterations, and their role in shaping intratumoral heterogeneity, adaptive potential, malignancy acquisition, and cancer progression. Particular emphasis is placed on the "just-right" dual nature of CIN, which can either drive tumor aggressiveness or precipitate mitotic catastrophe and cell death, depending on its magnitude and cellular context. By integrating cytogenetic, molecular, and evolutionary perspectives, this review highlights the relevance of these non-clonal interphase cytogenetic markers as sensitive indicators of genome instability and tumor dynamics. Understanding the interplay between clonal and non-clonal chromosomal alterations may provide valuable insights for the development of prognostic tools and therapeutic strategies aimed at exploiting the vulnerabilities of genomically unstable cancers.

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恶性肿瘤获得和癌症进展中染色体不稳定性的非克隆间期标志物。

染色体不稳定性（CIN）是癌症的普遍特征，也是肿瘤异质性、进化和治疗耐药性的主要驱动因素。CIN主要由染色体分离、DNA修复和有丝分裂保真度缺陷引起，促进肿瘤细胞群内持续的基因组多样化，使其能够对内在和外在的选择压力做出适应性反应。克隆性染色体改变反映了肿瘤进化过程中选择的稳定的基因组结构，而染色体不稳定性的非克隆间期标记则代表了捕捉正在进行的微进化动力学和基因组可塑性的短暂、低频事件。这篇综述提供了关于在间期评估CIN的经典和非经典标记的现有知识的综合，包括微核、核质桥、核芽、细胞质染色质、大量染色体分离错误、染色体断裂和基因组混乱相关现象。我们讨论了它们形成的细胞机制，它们对染色体结构和数量改变的贡献，以及它们在形成肿瘤内异质性、适应潜力、恶性获得和癌症进展中的作用。特别强调的是CIN的“恰到好处”的双重性质，根据其大小和细胞环境，它既可以驱动肿瘤侵袭性，也可以促成有丝分裂灾难和细胞死亡。通过整合细胞遗传学、分子遗传学和进化学的观点，本文强调了这些非克隆间期细胞遗传学标记作为基因组不稳定性和肿瘤动力学的敏感指标的相关性。了解克隆和非克隆染色体改变之间的相互作用可能为开发旨在利用基因组不稳定癌症脆弱性的预后工具和治疗策略提供有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.