Khavari et al. recently demonstrated that a significant fraction of one of the major forms of skin cancer (cutaneous squamous cell carcinomas) are associated with a mutated KNSTRN gene (a protein associated with the kinetochore). They identify a specific region of the gene as being a hotspot for UV induced mutation and suggest that these mutations may be an early event in the development of this type of skin cancer.(1)
Abstract from their nature paper (paywalled):
Here we report the discovery of recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN, which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). Cancer-associated KNSTRN mutations, most notably those encoding p.Ser24Phe, disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo. These findings suggest a role for KNSTRN mutagenesis in SCC development.(2)
My question: Scientists could theoretically alter the nucleotide sequence of the KNSTRN gene to remove the mutation hotspot, potentially lowering the incidence of this type of skin cancer. But are there any downsides to doing so? Are there any cases where a UV mutatable hotspot has shown to have some useful function in a cell or organism?