The major etiological agent in
skin cancer is exposure to UV-irradiation and the concomitant DNA damage. UV-induced DNA lesions, such as
thymine dimers, block
DNA synthesis by the major
DNA polymerases and inhibit the progression of DNA replication. Bypass of
thymine dimers and related lesions is dependent on the translesion
polymerase DNA polymerase eta (
Poleta). In the inherited disorder,
xeroderma pigmentosum variant (XPV), inactivation of
Poleta results in extreme sensitivity to UV light and a marked increase in the incidence of
skin cancer. Here, we tested the hypothesis that somatic mutations and/or polymorphisms in the POLH gene that encodes
Poleta are associated with the induction of UV-dependent
skin cancers. We sequenced the exonic regions of the
Poleta open reading frame in
DNA from 17 paired samples of squamous cell skin
carcinoma and adjacent histologically normal tissue. We analyzed approximately 120,000
nucleotides and detected no mutations in POLH in the
tumors. However, we identified 6 different single-nucleotide polymorphisms, 3 of them previously undocumented, which were present in both the
tumor and paired normal tissue. We conclude that neither mutations nor polymorphisms in the coding regions of POLH are required for the generation of human skin
squamous cell carcinoma.