Chromosomal Instability in Genome Evolution: From Cancer to Macroevolution

Abstract

The integrity of the genome is crucial for the survival of all living organisms. However, genomes need to adapt to survive certain pressures, and for this purpose use several mechanisms to diversify. Chromosomal instability (CIN) is one of the main mechanisms leading to the creation of genomic heterogeneity by altering the number of chromosomes and changing their structures. In this review, we will discuss the different chromosomal patterns and changes observed in speciation, in evolutional biology as well as during tumor progression. By nature, the human genome shows an induction of diversity during gametogenesis but as well during tumorigenesis that can conclude in drastic changes such as the whole genome doubling to more discrete changes as the complex chromosomal rearrangement chromothripsis. More importantly, changes observed during speciation are strikingly similar to the genomic evolution observed during tumor progression and resistance to therapy. The different origins of CIN will be treated as the importance of double-strand breaks (DSBs) or the consequences of micronuclei. We will also explain the mechanisms behind the controlled DSBs, and recombination of homologous chromosomes observed during meiosis, to explain how errors lead to similar patterns observed during tumorigenesis. Then, we will also list several diseases associated with CIN, resulting in fertility issues, miscarriage, rare genetic diseases, and cancer. Understanding better chromosomal instability as a whole is primordial for the understanding of mechanisms leading to tumor progression.

Tumor Evolution Is Directed by Cellular Responses to Survival Challenges

“…Increasing tumor heterogeneity is usually observed during tumor progression. Commonly, genomic instability has been viewed as the origin of tumor heterogeneity [1,2,14,15]. However, we argue, genomic instability is not the original cause for tumor heterogeneity; rather it is exploited to allow cells to rapidly respond to stressors by selecting variants with beneficial activity and function that enable them to successfully evolve advantageous capacities.…”

Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance

“…These include chromosomal breakage-fusion-bridge (BFB) cycles and a phenomenon known as chromothripsis, a dramatic restructuring of chromosomes. The chaos of CIN also gives rise to various unique chromosomal structures, such as micronuclei (MN), fold-back inversions, extrachromosomal DNA (ecDNA), and homogenously staining regions (HSRs), each potentially playing a role in cancer’s adaptability and resistance [ 149 ]. In conclusion, chromosomal instability is a driving force behind the phenotypic plasticity and resilience of cancer cells.…”

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

“…Aberrant chromosome numbers impact tumor suppressor genes, instigating drug resistance, particularly against topoisomerasetargeting agents [84][85][86][87]. Macro-evolutionary events, signified by substantial chromosomal alterations, contribute significantly to the development of drug resistance to topo-active agents [71,88].…”