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Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours

Oncogene volume 16, pages 30833086 (11 June 1998) | Download Citation

Subjects

Abstract

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.

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Affiliations

  1. Laboratoire de Cancérogénèse Expérimentale, UMR217 CNRS-CEA Radiobiologie Moléculaire et Cellulaire, 92265-Fontenay aux Roses, France

    • Sylvie Chevillard
    • , Céline Levalois
    •  & Jérôme Lebeau
  2. Laboratoire de Radiobiologie du DNA, Département de Radiobiologie et Radiopathologie, UMR217 CNRS-CEA Radiobiologie Moléculaire et Cellulaire, 92265-Fontenay aux Roses, France

    • J Pablo Radicella
    •  & Serge Boiteux
  3. Institut Curie, UMR147 CNRS, 75005-Paris, France

    • Marie-France Poupon
    •  & Bernard Dutrillaux
  4. Hôtel Dieu, Service d'Oncologie Médicale, 75004-Paris, France

    • Stéphane Oudard
  5. Département de Radiobiologie et Radiopathologie, CEA, 92265-Fontenay aux Roses, France

    • Bernard Dutrillaux

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Corresponding author

Correspondence to Serge Boiteux.

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DOI

https://doi.org/10.1038/sj.onc.1202096

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