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[Cancer Research 60, 4740-4744, September 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Alterations of the DNA Repair Gene OGG1 in Human Clear Cell Carcinomas of the Kidney1

Marc Audebert, Sylvie Chevillard, Céline Levalois, Gabor Gyapay, Annick Vieillefond, Jerzy Klijanienko, Philippe Vielh, Adel K. El Naggar, Stéphane Oudard, Serge Boiteux and J. Pablo Radicella2

Commissariat à l’Energie Atomique, Département de Radiobiologie et Radiopathologie [M. A., S. C., C. L., S. B., J. P. R.] and UMR217 Centre National de la Recherche Scientifique/Commissariat à l’Energie Atomique [M. A., S. B., J. P. R.], BP6, F92265 Fontenay aux Roses, France; Centre National de Séquençage, F94000 Evry, France [G. G.]; Département d’Anatomie et de Cytologie Pathologiques, Hôpital Cochin, F75014 Paris, France [A. V.]; Cytopathologie et Cytométrie Cliniques LRC/CEA #14, Institut Curie, F75248 Paris, France [J. K., P. V., A. K. E. N.]; and Service d’Oncologie Médicale, Hôtel Dieu, F95004 Paris, France [S. O.]

The OGG1 gene, which codes for a DNA repair protein with antimutator activity, is located on chromosome 3p25, a frequent site of allelic deletions in many types of human tumors, including renal clear cell cancers. We present the analysis of 99 renal tumors for alterations in the OGG1 gene to determine its association with tumorigenesis. Loss of heterozygosity in the 3p25 region was found for 85% of the informative cases. We detected somatic missense mutations of the OGG1 gene in 4 of the 99 tumor samples. Biochemical analysis of the mutant proteins revealed that a substitution at codon 46 impairs the enzymatic activity. We also describe the occurrence of several polymorphisms as well as aberrantly spliced OGG1 transcripts.




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