Tools used to assay genomic instability in cancers and cancer meiomitosis

Abstract

Genomic instability is a defining characteristic of cancer and the analysis of DNA damage at the chromosome level is a crucial part of the study of carcinogenesis and genotoxicity. Chromosomal instability (CIN), the most common level of genomic instability in cancers, is defined as the rate of loss or gain of chromosomes through successive divisions. As such, DNA in cancer cells is highly unstable. However, the underlying mechanisms remain elusive. There is a debate as to whether instability succeeds transformation, or if it is a by‐product of cancer, and therefore, studying potential molecular and cellular contributors of genomic instability is of high importance. Recent work has suggested an important role for ectopic expression of meiosis genes in driving genomic instability via a process called meiomitosis. Improving understanding of these mechanisms can contribute to the development of targeted therapies that exploit DNA damage and repair mechanisms. Here, we discuss a workflow of novel and established techniques used to assess chromosomal instability as well as the nature of genomic instability such as double strand breaks, micronuclei, and chromatin bridges. For each technique, we discuss their advantages and limitations in a lab setting. Lastly, we provide detailed protocols for the discussed techniques.

Clinically relevant fusion oncogenes: detection and practical implications

“…These mechanisms are absent in the somatic cells and re-emerge in cancer leading to translocations and aneuploidy. 35 – 38 …”

“…These mechanisms are absent in the somatic cells and re-emerge in cancer leading to translocations and aneuploidy. [35][36][37][38] One of mechanisms that promotes genomic instability is the so-called replication stress, that is, disturbances in the DNA replication process that lead to the arrest or destruction of the replication fork. 39 In turn, termination of replication in the absence of timely repair can provoke DNA double-strand breaks.…”

The Contributions of Cancer-Testis and Developmental Genes to the Pathogenesis of Keratinocyte Carcinomas

“…The most intuitive consequence of ectopic gene activation is a deregulation of cell differentiation pathways [ 3 ]. Activation of genes that are commonly restricted to prenatal development, including embryonic stem cell and fetal genes, is a hallmark of cancer cell de-differentiation to progenitor-like states and signifies differentiation impairment [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. When lineage-specific genes are expressed ectopically, trans-differentiation to an alternative cell lineage may be observed [ 6 , 7 , 8 , 9 , 10 , 11 ].…”

“…Activation of genes that are commonly restricted to prenatal development, including embryonic stem cell and fetal genes, is a hallmark of cancer cell de-differentiation to progenitor-like states and signifies differentiation impairment [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. When lineage-specific genes are expressed ectopically, trans-differentiation to an alternative cell lineage may be observed [ 6 , 7 , 8 , 9 , 10 , 11 ]. Additionally, the functions of ectopically-expressed genes may be recaptured in malignant contexts [ 12 , 13 ].…”

“…CTAs can be classified as X or non-X chromosome linked and further subdivided into various subfamilies. Their pathological relevance has been studied in a plethora of malignancies, including skin, lung, breast, gastrointestinal, genitourinary and hematological cancers [ 7 , 8 , 9 , 10 , 16 ]. Beyond their relevance to cancer immunology, ectopic CTA expression influences cancer cell biology, as their natural functions are often recaptured in a novel way to promote carcinogenesis.…”