Page "Spindle checkpoint" Paragraph 35

When the spindle checkpoint misfunctions, this can lead to chromosome missegregation, aneuploidy and even tumorigenesis.

Transformation occurs and is accelerated when maintenance of genomic integrity breaks down especially at the gross level of whole chromosomes or large portions of them.

In fact, aneuploidy is the most common characteristic of human solid tumors and thus the spindle assembly checkpoint might be regarded as a possible target for anti-tumour therapy.

This is a much underappreciated fact since mutations in specific genes known as oncogenes or tumor suppressor are primarily thought to be behind genetic instability and tumorigenesis.

Usually the various checkpoints in the cell cycle take care of genomic integrity via highly conserved redundant mechanisms that are important for maintaining cellular homeostasis and preventing tumorigenesis.

Several spindle assembly checkpoint proteins act both as positive and negative regulators to ensure the proper chromosome segregation in each cell cycle preventing chromosome instability ( CIN ) also known as genome instability.

Cytometric analysis of malignant carcinoma displaying aneuploidyGenomic integrity is now appreciated at several levels where some tumors display instability manifested as base substitutions, insertions, and deletions, while the majority displays gains or losses of whole chromosomes.