title: Understanding Xeroderma Pigmentosum Complementation Groups Using Gene Expression Profiling after UV-Light Exposure.
abstract: Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fold increase in skin cancers from age 2 and rarely live beyond 30 years. There are seven genetic subgroups of XP, which are all resultant of pathogenic mutations in genes in the nucleotide excision repair (NER) pathway and a XP variant resultant of a mutation in translesion synthesis, POLH. The clinical symptoms and severity of the disease is varied across the subgroups, which does not correlate with the functional position of the affected protein in the NER pathway. The aim of this study was to further understand the biology of XP subgroups, particularly those that manifest with neurological symptoms. Whole genome gene expression profiling of fibroblasts from each XP complementation group was assessed before and after UV-light exposure. The biological pathways with altered gene expression after UV-light exposure were distinct for each subtype and contained oncogenic related functions such as perturbation of cell cycle, apoptosis, proliferation and differentiation. Patients from the subgroups XP-B and XP-F were the only subgroups to have transcripts associated with neuronal activity altered after UV-light exposure. This study will assist in furthering our understanding of the different subtypes of XP which will lead to better diagnosis, treatment and management of the disease.
authors.affiliation: Hunter Medical Research Institute and the University of Newcastle, Callaghan, NSW 2289, Australia. nikola.bowden@newcastle.edu.au.
authors.forename: Nikola A
authors.initials: NA
authors.lastname: Bowden
authors.affiliation: Hunter Medical Research Institute and the University of Newcastle, Callaghan, NSW 2289, Australia. natalie.beveridge@newcastle.edu.au.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Beveridge
authors.affiliation: Hunter Medical Research Institute and the University of Newcastle, Callaghan, NSW 2289, Australia. katie.ashton@newcastle.edu.au.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Ashton
authors.affiliation: Hunter Medical Research Institute and the University of Newcastle, Callaghan, NSW 2289, Australia. katherine.baines@newcastle.edu.au.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Baines
authors.affiliation: Hunter Medical Research Institute and the University of Newcastle, Callaghan, NSW 2289, Australia. rodney.scott@newcastle.edu.au.|Hunter Area Pathology Service, Pathology NORTH, New Lambton Heights, NSW 2305, Australia. rodney.scott@newcastle.edu.au.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D004260:DNA Repair / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D059467:Transcriptome / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
keywords: UV; gene expression profile; nucleotide excision repair; transcriptome; xeroderma pigmentosum