The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin

  • Authors:
    • Annabelle M. Flanagan
    • Gerard Rafferty
    • Anne O'Neill
    • Leonie Rynne
    • Jack Kelly
    • Jack McCann
    • Michael P. Carty
  • View Affiliations

  • Published online on: April 1, 2007     https://doi.org/10.3892/ijmm.19.4.589
  • Pages: 589-596
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Skin cancer, the most common cancer in the general population, is strongly associated with exposure to the ultraviolet component of sunlight. To investigate the relationship between DNA damage processing and skin tumour development, we determined the POLH status of a cohort of skin cancer patients. The human POLH gene encodes DNA polymerase η (polη), which normally carries out accurate translesion synthesis past the major UV-induced photoproduct, the dithymine cyclobutane dimer. In the absence of active polη in xeroderma pigmentosum variant (XPV) patients, mutations accumulate at sites of UV-induced DNA damage, providing the initiating step in skin carcinogenesis. Forty patients diagnosed with skin cancer were genotyped for polymorphisms in the POLH protein-coding sequence, using glycosylase-mediated polymorphism detection (GMPD) and direct DNA sequencing of POLH PCR products derived from white blood cell genomic DNA. All individuals carried the wild-type POLH sequence. No POLH mutations were identified in genomic DNA from skin tumours derived from 15 of these patients. As determined by RT-PCR, POLH mRNA was expressed in all normal and skin tumour tissue examined. Polη protein was also detectable by Western blotting, in two matched normal and skin tumour extracts. An alternatively spliced form of POLH mRNA, lacking exon 2, was more readily detected in skin tissue than in white blood cells from the same patient. Real-time PCR was used to quantify POLH expression in matched normal and skin tumour-derived mRNA from a series of patients diagnosed with either basal or squamous cell carcinoma. Compared to matched normal skin tissue from the same patient, 1 of 7 SCC, and 4 of 10 BCC tumours examined showed at least a 2-fold reduction in POLH expression, while 1 of 7 SCC, and 3 of 10 BCC tumours showed at least a 2-fold increase in POLH expression. Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies between normal and skin tumours in the population under investigation. Knowledge of the POLH status in skin tumours could contribute to an understanding of the role of this gene in the development of the most common cancer in the general population.

Related Articles

Journal Cover

April 2007
Volume 19 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Flanagan AM, Rafferty G, O'Neill A, Rynne L, Kelly J, McCann J and Carty MP: The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin. Int J Mol Med 19: 589-596, 2007
APA
Flanagan, A.M., Rafferty, G., O'Neill, A., Rynne, L., Kelly, J., McCann, J., & Carty, M.P. (2007). The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin. International Journal of Molecular Medicine, 19, 589-596. https://doi.org/10.3892/ijmm.19.4.589
MLA
Flanagan, A. M., Rafferty, G., O'Neill, A., Rynne, L., Kelly, J., McCann, J., Carty, M. P."The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin". International Journal of Molecular Medicine 19.4 (2007): 589-596.
Chicago
Flanagan, A. M., Rafferty, G., O'Neill, A., Rynne, L., Kelly, J., McCann, J., Carty, M. P."The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin". International Journal of Molecular Medicine 19, no. 4 (2007): 589-596. https://doi.org/10.3892/ijmm.19.4.589