Proliferation and Clones

When a single cell is affected by a mutation that causes it to divide at an abnormally fast rate, the cancer process begins its devastating progression. As the cell starts to proliferate, it will give rise to clones of this originally mutated cell, each carrying the exact same mutation. This means that these clones will also divide more rapidly than any regular cell, leading to the outgrowth of normal cells by tumor cells.

There is a possibility that other mutations arise in some of these already mutated clonal cells, thereby enhancing their ability to divide and proliferate. These mutated clones might well overtake the initial tumor cells. This process may even repeat itself, adding another mutation to the clonal cells. This process, called the clonal evolution of tumor cells, leads to an increasingly aggressive tumor, proliferating faster and faster.

The Rate of Tumor Growth

The rate of this so-called clonal evolution of tumors depends primarily on the frequency with which the new mutations are acquired by the cells in the tumor. Any genetic defect that allows more mutations to arise, will subsequently accelerate the progression of the cancer.

For example, several genes that are responsible for the regulation of DNA repair, are often found to be affected by mutations in the cells of advanced tumors, and inherited disorders affecting DNA repair are usually closely linked with an increased risk of developing cancer. Since DNA repair mechanisms normally ‘fix’ the many of the mutations that occur in a cell, an inhibition in the DNA repair mechanisms will result in a higher likeliness for mutations to persist in all sorts of genes, including those that regulate cellular division.

Effect of Flawed Chromosome Segregation

Another possible factor that may contribute to the clonal evolution of tumors, are mutations that affect the segregation of the chromosomes. As a lot of cancer cell are aneuploid (containing an abnormal number of chromosomes, due to a flawed separation of the chromosomes during the cell division), it becomes clear how chromosome mutations can potentially contribute to the rapid progression of the cancer cells:

• Some genes (those that can be found on the extra chromosomes) are duplicated, and
• Other genes (those that were located on the missing chromosomes) are eliminated.

Such cellular defects that interfere with a regular chromosome separation, increase the occurrence of aneuploidy and as such they may accelerate the growth of the tumor(s) and the progression of the cancer.