Ultraviolet light-induced Mutation Drives Many Skin Cancers

According to researchers at the Stanford University School of Medicine, an ultraviolet (UV) light-induced genetic mutation is the probable culprit fueling countless human skin cancers.

The mutation occurs in the KNSTRN gene, which aids in equal distribution of DNA in cell division, and has been recently suggested to be one of the most commonly mutated oncogenes. Skin cancers have unique triggers compared with other cancers, and research has found that one simple mutation can act as a catalyst for a massive genomic alteration.

Having stayed under the radar thus far, “This previously unknown oncogene is activated by sunlight and drives the development of cutaneous squamous cell carcinomas,” according to Paul Khavari, MD, PhD, Carl J. Herzog Professor in Dermatology in the School of Medicine and chair of the Department of Dermatology. Experts have found KNSTRN mutations in nearly 20% of the more than 1 million new international cases of cutaneous squamous cell carcinoma annually reported, as well as in about 5% reports of melanoma.

Khavari and Carolyn Lee, MD, PhD, lead author of the study published in Nature Genetics, were in the midst of investigating the genetic causes of cutaneous squamous cell carcinoma, when they identified the unique mutation. Comparing DNA sequences within tumor cells and healthy skin, Khavari and Lee searched exclusively for mutations existing in the tumors. Among the 336 genes observed, the researchers initially found CDKN2A and TP53 as the predominant mutated genes linked to squamous cell carcinoma.

The two researchers discovered that the KNSTRN gene mutation resulted evidently from the replacement of the cytosine nucleotide with one called thymine, in a natural attempt for the cell to repair UV ray, particularly from sunlight, triggered damage. Khavari noted, “Mutations at this UV hotspot are not found in any of the other cancers we investigated. They occur only in skin cancers.”

As these new findings helped definitively link the correlation between skin cancer and sun exposure, further research can only aid in cultivating newer therapies.