Xeroderma pigmentosum and the role of UV-induced DNA damage in skin cancer.
Xeroderma pigmentosum and the role of UV-induced DNA damage in skin cancer.
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DOI：
10.1016/s1357-4310(98)01394-x
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发表时间：
1999-02
期刊：
影响因子：
--
通讯作者：
H. van Steeg;K. Kraemer
中科院分区：
文献类型：
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作者：
H. van Steeg;K. Kraemer
着色性干皮病(XP)是一种罕见的常染色体隐性遗传病，其特征是皮肤对阳光极端敏感。与正常人相比，XP患者在暴露在阳光下的皮肤区域患癌症的风险增加了1000多倍。遗传和分子分析表明，XP患者对紫外线(UV)诱导的DNA损伤的修复受到损害，这是由于构成DNA修复途径一部分的基因突变，该途径被称为核苷酸切除修复(NER)。另外两种疾病，Cockayne综合征(CS)和光敏性形式的毛发硫代营养不良(TTD)，与NER途径的缺陷有关。引人注目的是，尽管CS和TTD患者对紫外线敏感，但他们不会患皮肤癌。最近开发的模拟人类XP、CS和TTD表型的动物模型将有助于更好地理解这些疾病的病因以及紫外线诱导的DNA损伤在皮肤癌发生中的作用。
Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease that is characterized by the extreme sensitivity of the skin to sunlight. Compared to normal individuals, XP patients have a more than 1000-fold increased risk of developing cancer on sun-exposed areas of the skin. Genetic and molecular analyses have revealed that the repair of ultraviolet (UV)-induced DNA damage is impaired in XP patients owing to mutations in genes that form part of a DNA-repair pathway known as nucleotide excision repair (NER). Two other diseases, Cockayne syndrome (CS) and the photosensitive form of trichothiodystrophy (TTD), are linked to a defect in the NER pathway. Strikingly, although CS and TTD patients are UV-sensitive, they do not develop skin cancer. The recently developed animal models that mimic the human phenotypes of XP, CS and TTD will contribute to a better understanding of the etiology of these diseases and the role of UV-induced DNA damage in the development of skin cancer.