Mutant genes identified in battle against skin cancer

Researchers at Dundee University identified two genes which mutate in three quarters of all cases of cutaneous Squamous cell carcinoma (cSCC).

Unlike other common skin cancers, such as melanoma and basal cell carcinoma, the genes which are frequently mutated in cSCC have, until now, been unidentified.

Working in partnership with scientists at Harvard and the University of California in San Francisco, scientists in Dundee pinpointed two highly related genes and mutations which are thought to inhibit normal barrier development, important processes in both the skin and lungs.

Professor Irene Leigh, an expert in skin biology and disease, who led the Dundee end of the collaboration, said: “These gene mutations are a common factor in a form of skin cancer which is both common and life-threatening.

“By identifying these mutations, our group at Dundee, working with international partners, hopes to exploit the process of skin development to which these genes contribute to develop new cancer therapies capable of targeting skin and similar cancers such as lung SCC.”

Already one of the most common forms of cancer in the UK, the incidence of skin cancer is increasing. Most skin cancers are caused by too much ultraviolet (UV) radiation – the kind found in sunlight and sunbeds.

Squamous cell cancer is a form of non-melanoma skin cancer, of which it is estimated there are around 100,000 new cases in the UK every year. Commonly affecting areas of skin frequently exposed to the sun, it can spread to other parts of the body if left untreated. Squamous cell cancers appear as persistent, red, scaly spots, lumps, sores or ulcers, which may bleed easily.

The identified genes are known as “Notch” because when they were first identified in mutant fruit flies which had notches in their wings.

Dr Andrew South, a senior lecturer at the university, who was involved in the research, said: “These particular genes are involved in normal tissue differentiation and barrier formation. The cancers are switching them off.

“Now we know this, we can start hopefully switching them back on by identifying a drug which could do this. It’s a very significant development in terms of how we start thinking about therapies.”

Oliver Childs, senior science information officer at Cancer Research UK, added: “Knowing that Notch genes are involved in this type of skin cancer means that scientists can exploit this knowledge to find new treatments for the disease.

“As many of the gene faults found in this study are linked to damage caused by exposure to ultraviolet light, it also serves as an important reminder that people should stay safe in the sun to protect themselves from skin cancer.”

The research at Dundee was supported by Cancer Research UK and the European Research Commission. Details of the research have been published in the journal PNAS USA (Proceedings of the National Academy of Sciences).