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New Genetic Route to Skin Cancer

Armen Hareyan's picture

Skin Cancer Research

Cancer Research UK funded scientists at The Institute of Cancer Research have unravelled a complex chain of molecular triggers involved in the development of malignant melanoma, the deadliest form of skin cancer, a study published in Cancer Research reveals today.

The researchers discovered how a damaged version of a gene called RAS stimulates the growth of about 15-20 per cent of malignant melanomas.

Understanding more about the behaviour of those genes damaged by the sun that then cause skin cancer is important. In the future it will help scientists develop drugs to target individuals whose cancer developed as a result of a particular genetic fault.

Malignant melanoma, or melanoma, is the most serious type of skin cancer and because of the complicated molecular mechanism behind the disease, it often difficult to treat. And the number of people who get it in the UK is increasing.

Most skin cancers are caused by damage to genes from UV (ultraviolet) rays in sunlight. Melanoma occurs when melanocytes, the cells in the skin that protect us from UV light, grow uncontrollably.

The growth and behaviour of melanocytes are controlled by many different factors. Crucially, faults in the RAF genes are important because they send signals to the cell telling it to grow. Scientists already know that faults in the B-RAF gene are associated with around 50-70 per cent of melanomas.

However, until now it was not known how a growth signal was generated in the melanomas in which B-RAF is not mutated. This new research reveals that faults in the RAS gene activate another form of RAF, C-RAF, which then substitutes for B-RAF and so contributes to the development of melanoma.

Lead researcher Professor Richard Marais, from The Institute of Cancer Research, said: "We knew that RAS is mutated in up to a fifth of melanoma cases, but did not know how it was able to drive the growth of cancer cells. This research found that RAS activates one of the RAF proteins and from our previous work, we knew that a different RAF protein was implicated in the development of most other melanomas.

"Knowing more about the behaviour of all the different pathways involved in the development of melanoma could have implications for drug targeting. This discovery has the potential to enable us to develop targeted treatments to repair this particular fault and reverse the effects of the disease."

Professor John Toy, Cancer Research UK's medical director, said: "These findings will help improve our general understanding of how melanomas develop and grow out of control. Finding new treatments to effectively target melanoma is of critical importance because cases of the disease are set to treble over the next thirty years.

"It's important to remember that 80 per cent of malignant melanomas are due to excess exposure to the sun and these cases could be prevented if we protect ourselves from the harmful effects of the sun."

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In melanoma RAS mutations are accompanied by switching signalling from BRAF to CRAF and disrupted cAMP signalling. Dumaz et al. (2006). Cancer Research Vol 66 Issue 19.

This research was supported by Cancer Research UK and The Institute of Cancer Research.

Malignant melanoma

Malignant melanoma, also known as melanoma, is the most serious type of skin cancer. Every year around 8,000 cases of malignant melanoma are diagnosed in the UK. Malignant melanoma causes almost 1,800 deaths each year in the UK.

It usually develops in cells in the outer layer of the skin. The first visible signs of this may be a change in the normal look or feel of a mole.

Melanoma affects adults of all ages. It is one of the few cancers to affect young adults and is the third most common cancer amongst 15-39 year olds. However risk of this disease increases with age.

More women than men develop malignant melanoma. Melanomas in women are most common on the legs and in men they are most common on the back.

When melanoma is caught early it can be treated successfully. However, if a malignant melanoma is left it can spread to other parts of the body and may be fatal.

Non-malignant melanoma

Non-melanoma skin cancer is the most common and easily treated type of cancer. More than nine out of ten skin cancers are this type. There are over 65,000 new cases reported each year in the UK. Nine of out ten non-melanoma skin cancers are easily treatable and unlikely to spread.

These cancers are most common on areas of skin frequently exposed to the sun such as the head, neck, hands and forearms.

People most at risk of skin cancer tend to have: