MUTATIONS IN OGG1, A GENE INVOLVED IN THE REPAIR OF OXIDATIVE DNA-DAMAGE, ARE FOUND IN HUMAN LUNG AND KIDNEY TUMORS

The human OGG1 gene encodes a DNA glycosylase activity catalysing the excision of the mutagenic lesion 7,8-dihydro-8-oxoguanine from oxidati vely damaged DNA, The OGG1 gene was localized to chromosome 3p25, a re gion showing frequent loss of heterozygosity (LOH) in lung and kidney tumours. In this study, we have analysed by RT-PCR the expression of O GG1 in 25 small cell lung cancers, in 15 kidney carcinomas and the 15 normal kidney counterparts. The results show that OGG1 messenger RNA c an be detected in all tumours tested and that no significant differenc e was observed in the level of expression between normal and tumoral k idney tissues. Denaturing gradient gel electrophoresis (DGGE) was used to screen this series of human tumours for alterations in the OGG1 cD NA. The study revealed homozygous mutations in three tumours, two from lung and one from kidney, Sequencing analysis of the mutants identifi ed a single base substitution in each of the three cases: two tranvers ions (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 cours e of the multistage process of carcinogenesis in lung or kidney.