Table of Contents
In accordance with the definition provided by Yao and Dai (2014), genomic instability refers to elevated propensity of genome alteration in the course of cell division. The authors are emphatic that genome instability is characteristics of majority if not all cancer cells. They point out that cancer often stems from impairment to multiple genes responsible for regulating cell division and controlling cell division and polyp or tumor suppressors. On the other hand, genomic integrity is determined by close evaluation of mechanisms like mitotic changes, DNA damage, and DNA repair capacity. A flaw in the control of any of the latter mechanisms usually culminates in genomic instability that, in turn, makes cells susceptible to malignant change. Posttranslational alterations of the histone ends are closely linked to chromatin structure and cell cycle regulation. The status of DNA methylation also associated with genomic integrity.
Importance of Genetic Stability
Genomic stability maintenance is vital for cellular integrity, to prevent errors that could result from endogenous stress like reactive oxygen series (ROS), DNA replication, and external carcinogenic interferences like chemicals that damage DNA and ultraviolet light, among others. The most commonly accepted notion is that tumor formation and growth results from genomic transformation within originally normal cells. Consequently, tumor cell masses seem to exhibit greater genetic instability than normal ones. Extensive research has been channeled toward exploring genomic instability, in the effort to comprehend and regulate the formation and progression of tumors so as to aid in curbing cancer (Jeggo, Pearl & Carr, 2016).
Polyploidy to Aneuploidy and Genome Instability
Besides mutation of tumor suppressors or oncogene, a change to the number of chromosomes is linked to virtually all types of cancers. In regard to the chromosome perspective, several key points are worth noting. Normal body cells are diploid; meaning that they contain two complete chromosomes sets, one from either parent. When a cell loses or gains a single chromosome, aneuploidy occurs. The latter is responsible for some birth flaws and genetic disorders (Jeggo et al., 2016). On the other hand, when cells have duplicated genomes hence quadruple the number of chromosomes, tetraploidy is said to occur. This phenomenon results from failed cell division or fusion and is an antecedent of aneuploidy. Aneuploidy could also result from errors linked to chromosome segregation or contact with mutagens and is often observed in many cancer cases. According to Storchova & Pellman (2004), these aspects serve as proof of the idea that cancer cells resulting from aneuploidy could develop via tetraploidy intermediates. Therefore, with developments in identifying factors that support continued existence of tetraploid cells, eventually there could be potential in manipulating ploidy in human cells with the aim of fighting cancer.
Programmed Cell Death
Programmed cell death (PCD) is a genetically controlled process to get rid of damaged cells in the course of regular growth and development. Cancer development is fuelled by deregulated cell death. PCD is categorized on the basis of biochemical and morphological activities that take place in a cell. For instance, apoptosis occurs when the nuclear chromatin shrinks to cell margin, the cell condenses; the nucleus fragments and rounded outgrowths are formed on the plasma membrane. Ultimately, the outgrowths detach forming apoptotic bodies, which are engulfed by phagocytes forming internal compartments known as phagosomes resulting in complete removal of dead cells. Enhanced understanding of genomic stability, cell ploidy, and PCD could aid in further development of anti-cancer treatment approaches that will successfully eliminate growth of malignant tumors in cancer patients.
- Jeggo, P., Pearl, L., & Carr, A. (2016). DNA repair, genome stability and cancer: a historical perspective. Nature Reviews Cancer, 16, 35-42.
- Storchova, Z., & Pellman, D. From Polyploidy to Aneuploidy, Genome Instability and Cancer. Nature Reviews, Molecular Cell Biology, 5(1):45-54.
- Yao, Y. & Dai, W. (2014). Genomic Instability and Cancer. Journal of Carcinogenesis & Mutagenesis, 5, 165-176.