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Xeroderma Pigmentosum and Skin Cancer

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Molecular Mechanisms of Xeroderma Pigmentosum

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 637))

Abstract

The hypersensitivity of DNA repair deficient xeroderma pigmentosum (XP) patients to solar irradiation results in the development of high levels of squamous and basal cell carcinomas as well as malignant melanomas in early childhood. Indeed, XP presents a unique model for analysing the effects of unrepaired DNA lesions in skin carcinogenesis. The skin cancer predisposition, observed in XP patients, is due to the mutator gene activity of XP cells which lead to high levels of UV specific modifications of crucial regulatory genes in skin cells leading to cancer. Thus, the high levels of UV specific mutations, seen in oncogenes and tumor suppressor genes, which have been characterized in XP tumors, clearly demonstrate the major role of the UV component of sunlight in skin cancer development. The UV specific C to T and the tandem CC to TT UV signature transition mutations found in XP tumors are located at bipyrimidine sequences, the preferred UV targets in DNA. The same UV specific alterations are seen in key regulatory genes in sporadic skin cancers but at lower frequencies than those found in XP tumors.

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Author information

Authors and Affiliations

  1. Laboratory of Genetic Instability and Cancer, Institut Gustave Roussy, Villejuif, France

    Leela Daya-Grosjean

  2. Genomes and Cancer, FRE2939/CNRS, IFR54, Institute Gustave Roussy, 39, rue Camille Desmoulins, 94805, Villejuif Cedex, France

    Leela Daya-Grosjean

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  1. Leela Daya-Grosjean
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Editor information

Editors and Affiliations

  1. School of Science and Technology, Nottingham Trent University, Nottingham, England

    Shamim I. Ahmad MSc, PhD

  2. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan

    Fumio Hanaoka PhD

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© 2008 Landes Bioscience and Springer Science+Business Media

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Daya-Grosjean, L. (2008). Xeroderma Pigmentosum and Skin Cancer. In: Ahmad, S.I., Hanaoka, F. (eds) Molecular Mechanisms of Xeroderma Pigmentosum. Advances in Experimental Medicine and Biology, vol 637. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09599-8_3

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