Introduction

The genome is an organism’s complete set of DNA and is organized into chromosomes containing genes that encode for hereditary traits. As our cells grow reproduce and die, DNA is repeatedly replicated and repaired and bits and pieces of its sequences are changed in the process, thus producing mutations. These mutations create genetic variation and it is proven that genetic mutation is key to our evolution and survival. But mutations are not always beneficial, they can be harmful leading to genetic diseases. When these mutations occur in an increased levels genetic instability takes place.

Definition

Genomic instability refers to an increased tendency of alterations in the genome during the life cycle of cells. It is a major driving force for tumorigenesis. During a cell division, genomic instability is minimized by four major mechanisms: high-fidelity DNA replication in S-phase, precise chromosome segregation in mitosis, error free repair of sporadic DNA damage, and a coordinated cell cycle progression.

Types of genomic instabilities

• Nucleotide Instability
• Microsatellite Instability
• Chromosomal Instability

Causes of genomic instability

• DNA Replication Defects. ...
• Fragile Sites. ...
• Transcription-associated instability. ...
• Increase Genetic Variability. ...
• Low frequency of mutations without cancer. ...
• Cause of mutations in cancer. ...
• Very frequent mutations in cancer. ...
• Cause of high frequency of mutations in cancer.

Methods to detect genomic instability

Single cell approach

• Karyotyping
• Fluorescence in-situ hybridization
• Single cell sequencing
• Multiple annealing
• Looping based amplification

Multiple cell approach

• Flow cytometry
• Array comparative genomic hybridization
• SNP arrays
• Polymerase chain reaction

Pathways to prevent genomic instability in cancer

• DNA Damage Check Point
• DNA Repair Pathway
• Mitotic Checkpoint
• Telomere Maintenance

Conclusion

Genomic instability is a characteristic of most cancer cells. It is an increased tendency of genome alteration during cell division. Cancer frequently results from damage to multiple genes controlling cell division and tumor suppressors. It is known that genomic integrity is closely monitored by several surveillance mechanisms, DNA damage checkpoint, DNA repair machinery and mitotic checkpoint. A defect in the regulation of any of these mechanisms often results in genomic instability, which predisposes the cell to malignant transformation. Posttranslational modifications of the histone tails are closely associated with regulation of the cell cycle as well as chromatin structure. Nevertheless, DNA methylation status is also related to genomic integrity. We attempt to summarize recent developments in this field and discuss the debate of driving force of tumor initiation and progression.

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