Genomic instability refers to an increased tendency of an organism’s DNA or genome to acquire mutations. It is a hallmark of many cancers and other diseases and can be influenced by many factors, both genetic and environmental.
The integrity of the genome is crucial for the normal functioning and survival of cells. Cells have many mechanisms to repair DNA damage and maintain genomic stability. These include DNA repair systems, cell cycle checkpoints, and apoptosis (programmed cell death), which can eliminate cells with severe DNA damage that cannot be repaired.
However, when these mechanisms are compromised due to mutations or other factors, DNA damage can accumulate, leading to genomic instability. This can manifest in many forms, including:
- Base substitutions: Changes in the individual nucleotides that make up DNA.
- Insertions or deletions: The addition or removal of segments of DNA.
- Copy number variations (CNVs): Duplications or deletions of large segments of DNA, which can include one or more genes.
- Chromosomal rearrangements: Larger-scale changes in the structure of chromosomes, such as translocations (where parts of different chromosomes are swapped), inversions (where a segment of a chromosome is reversed), or aneuploidy (where whole chromosomes are added or lost).
Genomic instability can lead to changes in gene function and regulation that drive the development and progression of diseases, including cancer. For example, it can lead to the activation of oncogenes (genes that promote cell growth and proliferation) or the inactivation of tumor suppressor genes (genes that normally prevent uncontrolled cell growth).
Understanding the causes and consequences of genomic instability is a major focus of research in cancer biology and other fields, and it can inform the development of new therapies and preventive strategies. For example, some cancer treatments are designed to exploit the genomic instability of cancer cells to selectively kill these cells while sparing normal cells.
