Genetic Mutations and Skin Cancer

By Jane Farrell

Researchers have found that millions of skin cancers may be caused by a combination of a genetic mutation and ultraviolet light.

A study by investigators from the Stanford University School of Medicine found that the mutation occurs in a gene called KNSTRN, which helps cells divide their DNA during cell division.

KNSTRN is an oncogene – a gene that causes cancer when mutated. The new research indicates that it may be one of the most commonly mutated oncogenes in the world.

“This…oncogene is activated by sunlight and drives the development of cutaneous squamous cell carcinomas,” said Paul Khavari, MD, PhD, the Carl J. Herzog Professor in Dermatology in the School of Medicine and chair of the Department of Dermatology. “Our research shows that skin cancers arise differently from other cancers, and that a single mutation can cause genomic catastrophe.”

More than 1 million cases of cutaneous squamous cell are diagnosed annually worldwide. It is the second most common cancer in humans. The researchers found that KNSTRN is a factor in about 20 percent of cutaneous squamous cell carcinomas and in about 5 percent of melanomas, another form of skin cancer.

The mutation in the KNSTRN gene is linked to a cell’s unsuccessful attempt to repair itself after suffering damage from high-energy ultraviolet rays, such as those found in sunlight.

“Mutations at this UV hotspot are not found in any of the other cancers we investigated,” said Khavari. “They occur only in skin cancers.”

The findings were published in the journal Nature Genetics. Khavari and lead author Carolyn Lee, MD, PhD, plan to study 336 additional mutated genes.