A mutation in the PTEN gene has varied and sometimes serious consequences because when it is working properly PTEN plays several important roles in our cells.
Like many things in nature, the cells in our body go through a life cycle – they are created, they do their job and they die. In fact, each of us makes millions of new cells every second to replace the ones that have died. To create these new cells, existing cells replicate and split in two, a tightly-controlled process known as cell division.
However, things can also go wrong if cell division happens too rapidly or without the correct control mechanisms. If too many cells are produced, this can lead to overgrowth of tissues.
Also, every time a cell divides, errors can occur in the cell’s DNA. Normal cells have tools to correct these errors but if these mechanisms don’t work properly, this can lead to the accumulation of errors which may eventually lead to the formation of cancerous tumours.
To ensure the correct balance is achieved, cell division is tightly controlled by hundreds of genes. The molecules these genes produce signal to each other when to create more cells and when to put the brakes on.
This is where PTEN comes in. In its usual form, the PTEN gene creates one of these molecules - an enzyme that both stops cell division and triggers a process that removes damaged cells by making them self-destruct. Because this helps keep cell division in check, reducing the likelihood that tumours will form, PTEN is often referred to as a tumour suppressor gene.
In addition, PTEN is involved in cell growth and some evidence suggests that it helps protect the DNA in our cells from damage, which again helps prevent the development of tumours. For this reason, PTEN is sometimes called a guardian of our genome.
It is important to note that it is not fully understood how these various roles that PTEN plays contribute to the symptoms of PHTS. This is an active area of research.
Everyone carries two copies of the PTEN gene in their cells, one inherited from each parent. In people with PHTS, one of these copies is altered. This can result in the gene not working at all, not working very well or working in a different way.
Whatever the exact mechanism, the consequence is that the normal brakes on cell division and growth don’t work as well as they should. This leads to an overgrowth of tissues. This can cause the lumps and bumps that give PHTS its name, as well as changes in the structure of the brain which may contribute to people having a larger than average head.
Uncontrolled cell division also increases the chances that malignant tumours will develop. However, this doesn’t mean that if you carry a mutated PTEN gene you will get cancer - it raises the likelihood. Many other gene mutations have to occur before the conditions are right for a lump of cells to turn into a cancerous tumour.
It is impossible to say what causes any individual’s gene – PTEN or otherwise – to become altered. Genes mutate for many reasons, for example, when cells divide incorrectly and are repaired imperfectly, or when chemicals in the environment damage DNA.
What we do know is that the PTEN mutation occurs in the DNA of sperm or egg cells. This means that if you carry a faulty gene, you will either have inherited it from a parent who carried it in their sperm or egg cells – this is the case for between 50 and 90 percent of people with PHTS – or the mutation will have spontaneously occurred in the sperm or the egg.
Either way, as the fertilised egg divided, each resulting cell in the growing embryo has the PTEN mutation. If the mutation happened spontaneously after fertilisation, you will be the first person in your family to have the faulty gene but you will be able to pass it on to any children of your own.