Each cell in the body divides a finite number of times. During each cell division a complex series of events takes place inside the cell, which ensures that each daughter cell is an exact genetic replica of the parent.
These events are orchestrated by master genes, which produce proteins that act as gatekeepers at the checkpoints between the different phases of the cell cycle.
How the gatekeeper genes work –
Functional tumour suppressor genes are critical in ensuring that the cell cycle runs smoothly. If an error is made during one of the phases in the cell cycle, the tumour suppressor genes apply the brakes to the cell cycle, and do not allow the cycle to continue unless the damage has been repaired. In case the damage is non-reversible, the tumour suppressor genes trigger the pre-programmed suicide cycle – called apoptosis – within the cell.
This ensures that damaged cells with defective DNA or protein are not able to propagate within the body.
By default, tumour suppressor genes are switched ‘ON’ all the time. Each one of us has two copies of this gene, one on each chromosome. A mutation may cause one of the copies to become non-functional, but this may not necessarily lead to cancer as the second copy of the gene is still functional. A mutation in the second copy, however, does not bode well for the cell. It effectively removes any brakes on the cell cycle, allowing damaged cells to continue to divide before the damage is repaired.
Over time, the proportion of damaged cells in relation to healthy cells increases. These defective cells may then start to grow rapidly and out-compete neighbouring ‘healthy’ cells for oxygen, glucose and other nutrients. This mass of cells is called a tumour. A tumour is benign if the cell growth is self-limiting. However, in some cases, the cells continue to grow indefinitely, and at a faster rate than normal cells – this is a malignant tumour, or cancer. If the malignant cells enter the lymphatic system and spread around the body, the cancer is said to have metastasised.
Common examples of tumour suppressor genes include TP53 and BRCA-1 and BRCA-2. Over half of human cancers are linked to defective p53 protein produced by the TP53 gene. BRCA-1 and BRCA-2 are linked to early-onset breast cancer and ovarian cancer. In very rare instances, children may be born with defective p53 genes, greatly increasing their susceptibility to cancer – this is called the Li-Fraumeni-Syndrome.