Xeroderma pigmentosum: from symptoms and genetics to gene-based skin therapy.
Xeroderma pigmentosum (XP) is a rare, recessively inherited genodermatosis prone to ultraviolet (UV)-induced skin neoplasms from keratinocyte origin, i.e. basal and squamous cell carcinoma. Cells from classic XP patients fail to properly eliminate UV-induced DNA lesions by the nucleotide excision repair (NER) mechanism. A variant form of XP, called XP-V suffers from faulty translesion synthesis. We review here recent data on XP gene products whose alterations affect NER and result in one of the 7 complementation groups of XP. Encouraging results of retrovirus-based genetic correction of XP keratinocytes are summarized and support realistic prospects of gene therapy for the XP-C complementation group.
Magnaldo
Thierry
T
Laboratory of Genetic Instability and Cancer, CNRS UPR2169, Institut Gustave Roussy, Villejuif, France. magnaldo@igr.fr
Sarasin
Alain
A
D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D012878:Skin Neoplasms / Q000517:prevention & control; D014466:Ultraviolet Rays / Q000009:adverse effects; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*