Frequent allelic loss at chromosome 3p distinct from genetic alterations of the 8-oxoguanine DNA glycosylase 1 gene in head and neck cancer.
Cigarette smoking is the major known risk factor for head and neck cancer. Tobacco promotes oxidative stress and enhances tissue levels of 8-hydroxyguanine (8-OH-G) in smokers. The presence of 8-OH-G does not impede replication but leads to an accumulation of G-->T transversions. Recently, the gene for human 8-oxoguanine DNA glycosylase 1 (hOGG1), an enzyme involved in the repair of 8-OH-G in humans, was cloned and mapped to chromosome 3p. In head and neck tumors, the hOGG1 gene locus is often targeted by loss of heterozygosity (LOH), and the spectrum of mutations in the p53 gene shows a bias in favor of G:C-->T:A transversions, as would be expected if HOGG1 repair functions were disabled. To test the involvement of hOGG1 in head and neck carcinogenesis, we had previously screened 56 tumors for LOH at 3p. From these tumors and two others, we selected 33 tumors demonstrating LOH for further mutational analysis of this gene. No somatic inactivating mutation was found in hOGG1. Polymorphisms involving intron 4 and exon 7 were present in 30% of the patients. A new polymorphism was identified in one patient in exon 6 and led to the amino-acid change G308E. Similar repair activities were found for the wild-type and exon 6-variant enzymes. Therefore, the involvement of hOGG1 in head and neck carcinogenesis is not strongly supported by this work.
Blons
H
H
Laboratoire de Toxicologie Moléculaire, Université René Descartes, Paris, France.
Radicella
J P
JP
Laccourreye
O
O
Brasnu
D
D
Beaune
P
P
Boiteux
S
S
Laurent-Puig
P
P
D000483:Alleles; D019943:Amino Acid Substitution; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D005091:Exons; D005784:Gene Amplification; D005819:Genetic Markers; D014644:Genetic Variation; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D019656:Loss of Heterozygosity; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D011110:Polymorphism, Genetic
D005819:Genetic Markers; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase