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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >High levels of patched gene mutations in basal-cell carcinomas from patients with xeroderma pigmentosum
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High levels of patched gene mutations in basal-cell carcinomas from patients with xeroderma pigmentosum

机译：色素干皮症患者基底细胞癌中高水平的修补基因突变

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Recently, hptc, a human gene homologous to the Drosophila segment polarity gene patched (ptc), has been implicated in the nevoid basal-cell carcinoma (BCC) syn- drome, and somatic mutations of hptc also have been found in sporadic BCCs, the most frequent cancers found in the white population. We have analyzed the hptc gene, postulated to be a tumor suppressor gene, in 22 BCCs from patients with the hyperphotosensitive genodermatosis xeroderma pigmento- sum (XP). Patients with XP are deficient in the repair of UV-induced DNA lesions and are characterized by their predisposition to cancers in sun-exposed skin. Analysis using PCR-single-strand conformation polymorphism of the hptc gene identified 19 alterations in 16 of 22 (73) of the BCCs examined. Only two (11) deletions of the hptc gene were found in XP BCCs compared with >30 rearrangement observed in non-XP sporadic BCCs, and 17 of 19 (89) were base substitutions. Among the 17 base substitutions, 11 (65) were CC -> TT tandem mutations, and 4 (23) were C -> T substitutions, all targeted at bipyrimidine sites. Hence, a significantly higher number (15 of 19; 79) of UV-specific alterations are seen in XP tumors, in contrast to non-XP sporadic BCCs. Interestingly, we have found that in 7 of 14 (50) XP BCCs analyzed, both hptc and the tumor suppressor gene p53 are mutated. Not only have our data indicated the key role played by hptc in the development of BCCs, they also have substantiated the link between unrepaired UV-induced DNA lesions and skin carcinogenesis, as exemplified by the UV- specific alterations of differen
机译：最近，与果蝇节段极性基因补丁（ptc）同源的人类基因hpctc与空洞的基底细胞癌（BCC）综合征有关，并且在零星的bcc中也发现了hpctc的体细胞突变。在白人人群中发现最常见的癌症。我们已经分析了22例患有高光敏性皮肤病干性色素病（XP）患者的BCC中的hptc基因，该基因被认为是抑癌基因。 XP患者缺乏紫外线诱发的DNA损伤的修复功能，其特征是易受阳光照射的皮肤中的癌症。使用hptc基因的PCR单链构象多态性进行的分析确定了所检查的BCC中22个中的16个（73）中有19个改变。与在非XP散发性BCC中观察到的> 30重排相比，在XP BCC中仅发现了两（11）个hptc基因缺失，而19（89）个中的17个是碱基取代。在这17个碱基取代中，有11个（65）是CC-> TT串联突变，有4个（23）是C-> T取代，均针对联嘧啶位点。因此，与非XP散发性BCC相比，在XP肿瘤中观察到明显更多的UV特异性改变（19个中的15个； 79个）。有趣的是，我们发现在分析的14（50）个XP BCC中有7个hptc和抑癌基因p53均发生了突变。我们的数据不仅表明hptc在BCC的发展中起着关键作用，而且还证实了未修复的UV诱导的DNA损伤与皮肤致癌之间的联系，例如不同的UV特异性改变就是例证。

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