Genetic mutation in KRAS gene can trigger melanoma

23 June 2010

A genetic mutation found in some malignant melanomas can initiate development of this most deadly form of skin cancer, according to a study published in the journal Cancer Research.

The gene KRAS was already known to be mutated in about two per cent of malignant melanomas, but the new study by The Institute of Cancer Research (ICR) is the first to show that damage to this gene can be the first in a procession of genetic events necessary to trigger malignant melanoma.

“We know that the main cause of skin cancer is damage driven by the UV rays in sunlight, and we are now building up a picture of the key genes involved in this disease,” lead author Professor Richard Marais from the ICR says.

“We have already discovered that mutations in another gene, BRAF, could drive up to half of melanomas, and now we’ve established that damage to the KRAS gene can also be the first step in malignant melanoma development. Ultimately, these discoveries will help us design more effective treatments for malignant melanoma.”

The incidence of malignant melanoma is increasing in the UK, with around 10,000 people diagnosed and 2,300 deaths a year. The disease is difficult to treat once it has spread to other organs.

RAS genes normally control cell growth during development and other processes such as wound healing, but they can stimulate cancer development when they malfunction. There are three RAS genes in humans and previous research has shown that the other two, HRAS and NRAS, can trigger melanoma growth in mice, but no studies have been reported for KRAS.

In a study funded by the ICR, Cancer Research UK and Breakthrough Breast Cancer, scientists created an animal model that mimicked how humans acquire mutations in KRAS. The results demonstrated that KRAS mutations can be the first event in melanoma development, but other genetic mutations are thought to be necessary to promote cancer growth. It is hoped that the identification of these other changes will allow new therapeutic approaches to be developed.

Dr Helen George, head of science information at Cancer Research UK, said: “The results from this study are very encouraging as they add to our knowledge of the key genetic events that can cause skin cancer to develop. Understanding what triggers the disease will help scientists discover better treatments.

“It’s important to remember that most skin cancers are caused by overexposure to the sun or sunbeds. By taking care not to burn and enjoying the sun safely, most cases of the disease could be prevented.”