A Mutated Gene Which Causes Cancer
The adult human body is estimated to contain a total of 37 trillion cells. We have all arisen from a single fertilised cell by many rounds of cell division, giving firstly 2, then 4, then 8, then 16 cells and so forth. Once we have reached adult size, cell division is then tightly regulated to maintain the correct number of cells at the appropriate anatomical site. Any remaining cell division is balanced to only replace worn out or damaged cells. In cancer this tight regulation goes awry.
Cancer arises from damage to our DNA which results in a particular cell type undergoing continuous and uncontrolled cell division. In this way an excess of unnecessary and unwanted cells accumulates in the body. Over the last 50 years or so, cancer research has revealed that it is mutation in certain specific genes which drives the development of cancers. These genes are called oncogenes.
One instance of such genes are the set of three which carry the instructions to make normal variants of a protein called Ras. The Ras proteins act as signalling switches within our cells. Cells from time to time receive activating signals from within the body. When these become strong and prolonged, they can trigger the cell to start dividing and to become highly active. Ras has a role in transmitting such signals from the outside of the cell to its central nucleus, in which all our genes are stored.
Normally Ras flickers on and off according to these signals, as its structure is switched rapidly between active and inactive states, rather like a controlling circuit within a complex electronic device. However there are certain tiny errors, or mutations, which can occur within the Ras genes. Some of these then cause the Ras proteins they produce to be permanently locked into the ‘on’ state. If this happens, the signalling circuit which Ras participates in is permanently active and the cell is driven to undergo cell division without ceasing, producing more and more overactive cells.
Ras mutations are found in around one quarter of all human cancers, although the proportion varies greatly from one cancer type to another. For instance some 90% of pancreatic cancers contain mutations in a Ras gene, whereas other cancers show very little. With modern gene sequencing techniques, it is straight forward to find out whether the cancer in an individual patient has the Ras mutations, or not.
Cancer researchers are now trying to find ways of switching off excess Ras signalling in those cancers containing these mutations, but the challenge of being able to do this effectively and safely has so far proved elusive.
Ras is just one of several well-established oncogenes which can cause cancer when they are mutated.