Genomic instability refers to a high frequency of mutations within the genome of a cellular lineage. This can include small-scale changes, such as point mutations, insertions, or deletions of bases, as well as large-scale changes, such as duplications, translocations, inversions, and deletions of larger segments of DNA.

Genomic instability is a hallmark of cancer and plays a key role in its development and progression. Normal cells have a variety of mechanisms to maintain genomic stability, including DNA repair pathways, cell cycle checkpoints, and programmed cell death (apoptosis). When these mechanisms are compromised, for example due to inherited or acquired mutations in the genes involved in these pathways, this can lead to genomic instability.

Genomic instability can provide the genetic diversity that fuels evolution and adaptation in populations of cells. In the context of cancer, this can lead to the development of subpopulations of cells with new or enhanced capabilities, such as increased proliferation, resistance to apoptosis, or the ability to invade and metastasize. This makes genomic instability a major challenge in cancer treatment, as it can lead to the development of resistance to therapy.

Understanding the mechanisms that contribute to genomic instability and how to counteract them is a major focus of cancer research. Strategies to target cells with high levels of genomic instability, or to enhance the cell’s own mechanisms for maintaining genomic stability, are being explored as potential cancer therapies.