title: Mutations in DNA polymerase eta are not detected in squamous cell carcinoma of the skin.
abstract: 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.
authors.affiliation: The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, USA.
authors.forename: Eitan
authors.initials: E
authors.lastname: Glick
authors.forename: Lisa M
authors.initials: LM
authors.lastname: White
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Elliott
authors.forename: Daniel
authors.initials: D
authors.lastname: Berg
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Loeb
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D017931:DNA Primers; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics*; D044465:White People; D000099270:Y-Family DNA Polymerases
chemical_list: D017931:DNA Primers; D004259:DNA-Directed DNA Polymerase; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases