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