Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours
Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours
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DOI：
10.1038/sj.onc.1202096
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发表时间：
1998-06-11
期刊：
影响因子：
8
通讯作者：
Boiteux, S
中科院分区：
文献类型：
--
作者：
Chevillard, S;Radicella, JP;Boiteux, S
人类 OGG1 基因编码 DNA 糖基化酶活性，催化从氧化损伤的 DNA 中切除诱变病变 7,8-二氢-8-氧代鸟嘌呤。 OGG1 基因定位于染色体 3p25，该区域在肺和肾肿瘤中频繁出现杂合性丢失 (LOH)。在本研究中，我们通过 RT-PCR 分析了 25 例小细胞肺癌、15 例肾癌和 15 例正常肾癌中 OGG1 的表达。结果显示，在所有测试的肿瘤中均可检测到OGG1信使RNA，并且正常肾组织和肿瘤肾组织之间的表达水平没有观察到显着差异。使用变性梯度凝胶电泳 (DGGE) 筛选这一系列人类肿瘤中 OGG1 cDNA 的变化。该研究揭示了三种肿瘤中的纯合突变，两种来自肺，一种来自肾，对突变体的测序分析在三种情况下均发现了单碱基替换：两种颠换（GC 至 TA 和 TA 至 AT）和一种转换（GC 至 AT），所有三种替换均导致 hOgg1 蛋白中的氨基酸变化。对于突变肾肿瘤，正常组织对应物显示出野生型特征。这些结果表明 OGG1 突变在肺或肾癌发生的多阶段过程中发挥作用。
The human OGG1 gene encodes a DNA glycosylase activity catalysing the excision of the mutagenic lesion 7,8-dihydro-8-oxoguanine from oxidatively damaged DNA, The OGG1 gene was localized to chromosome 3p25, a region showing frequent loss of heterozygosity (LOH) in lung and kidney tumours. In this study, we have analysed by RT-PCR the expression of OGG1 in 25 small cell lung cancers, in 15 kidney carcinomas and the 15 normal kidney counterparts. The results show that OGG1 messenger RNA can be detected in all tumours tested and that no significant difference was observed in the level of expression between normal and tumoral kidney tissues. Denaturing gradient gel electrophoresis (DGGE) was used to screen this series of human tumours for alterations in the OGG1 cDNA. The study revealed homozygous mutations in three tumours, two from lung and one from kidney, Sequencing analysis of the mutants identified a single base substitution in each of the three cases: two tranversions (GC to TA and TA to AT) and one transition (GC to AT), All three substitutions cause an amino acid change in the hOgg1 protein. For the mutant kidney tumour, the normal tissue counterpart shows a wild-type profile, These results suggest a role for OGG1 mutations in the course of the multistage process of carcinogenesis in lung or kidney.