Tuesday, September 23, 2014
The association between sun exposure and skin cancer is well-known. Results from a recent study further cement this association by showing that UV rays from the Sun can turn a unknown gene into an oncogene. It is thought that this genetic mutation might be responsible for causing millions of human skin cancers.
This study was published in Nature Genetics and has reported that the oncogene KNSTRN, which was unknown till date, gets activated by the sunlight and triggers the development of cutaneous squamous cell carcinoma. The researchers stumbled upon this discovery when they were combing through DNA sequences of genes from tumor cells with those of normal skin and were looking for mutations that occurred only in tumors.
Apart from the usual suspects such as, CDKN2A and TP53, the researchers also found that KNSRTN to be mutated in about 20% of cutaneous squamous cell carcinoma and 5% of melanomas. The researchers also found KNSRTN mutation in about 20% of cases of actinic keratoses, which is a premalignant condition that often leads to squamous cell carcinoma, but none in normal skin samples.
The researchers further extended their observation of the ability of the mutant KNSRTN gene to cause cancers in a mouse model of squamous cell carcinoma. They also found KNSRTN to be mutated in patient derived samples of squamous cell carcinoma and patients with this mutation had severely abnormal genomes.
The study found that the mutation in the KNSRTN gene was caused due to the swapping of a single nucleotide cytosine with thymine within a specific short stretch of DNA. The swap was indicative of a cell’s attempt to repair damage from high-energy UV rays such as that in sunlight.
The importance of this finding is reiterated by Dr. Khavari, a co-investigator of the study, “Mutations of this UV hotspot are not found in any of the other cancers we investigated. They occur only in skin cancers.”
The KNSTRN gene is involved in helping cells divide their DNA equally during cell division. If the chromosomes don’t separate equally during cell division, the daughter cells will have extra or missing chromosomes and are known as aneuploid. It is well-known that aneuploidy is a critical early step towards the development of many types of cancers.
Results from this study will help researchers to understand the development of these types of skin cancers and also help them to develop new therapies. It also brings into focus the importance of protecting ones skin from sun exposure as even a single gene mutation can spell cause genomic catastrophe.
For study details:-Click Here!