title: Six genes associated with the clinical phenotypes of individuals with deficient and proficient DNA repair.
abstract: Xeroderma pigmentosum (XP) is a genetic disorder characterised by hypo-/hyperpigmentation, increased sensitivity to ultraviolet (UV)-radiation and an up to 2000-fold increased skin cancer risk. Cells from XP-patients are defective in nucleotide excision repair (NER) responsible for repair of UV-induced DNA damage. This defect accounts for their mutator phenotype but does not predict their increased skin cancer risk. Therefore, we carried out array analysis to measure the expression of more than 1000 genes after UVB-irradiation in XP cells from three complementation groups with different clinical severity (XP-A, XP-D, XP-F) as well as from patients with normal DNA repair but increased skin cancer risk (≥2 basal or squamous cell carcinoma at age <40yrs). Of 144 genes investigated, 20 showed differential expression with p < 0.05 after irradiation of cells with 100 mJ/cm(2) of UVB. A subset of six genes showed a direct association of expression levels with clinical severity of XP in genes affecting carcinogenesis relevant pathways. Genes identified in XP cells could be confirmed in cells from patients with no known DNA repair defects but increased skin cancer risk. Thus, it is possible to identify a small gene subset associated with clinical severity of XP patients also applicable to individuals with no known DNA repair defects.
authors.affiliation: Institut für Umweltmedizinische Forschung at the Heinrich-Heine-University gGmbH, Auf'm Hennekamp 50, D-40225 Düsseldorf, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gremmel
authors.forename: Susanne
authors.initials: S
authors.lastname: Wild
authors.forename: Winfried
authors.initials: W
authors.lastname: Schuller
authors.forename: Viola
authors.initials: V
authors.lastname: Kürten
authors.forename: Klaus
authors.initials: K
authors.lastname: Dietz
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.forename: Mark
authors.initials: M
authors.lastname: Berneburg