Frequent allelic imbalance and loss of protein expression of the DNA repair gene hOGG1 in head and neck squamous cell carcinoma

Reactive oxygen species produced by aerobic cellular metabolism or through exposure to environmental carcinogens can cause oxidative DNA damage by gen erating DNA base lesions and strand breakage. Prime among these base lesion s is the conversion of guanine to 8-oxoguanine. Among 20 or so oxidative DN A base lesions, 8-oxoguanine is the most abundant and is critical in terms of mutagenesis because it is capable of mispairing with adenine, which, if not sufficiently repaired, may lead to G:C to T:A transversion upon DNA rep lication. The gene encoding human 8-oxoguanine DNA glycosylase 1 (hOGG1), c apable of excision repair of 8-oxoguanine, has been recently cloned, charac terized, and mapped to the short arm of chromosome 3 (3p25-26), a region sh owing frequent loss of heterozygosity (LOH) in head and neck squamous cell carcinoma (HNSCC). In the present study, we developed a tissue microdissect ion approach designed for use with formalin-fixed, paraffin-embedded specim ens which is capable of detecting and characterizing the hOGG1 allelic loss using two highly informative, intragenic single nucleotide polymorphisms. Among 45 cases of HNSCC, 18 cases were informative. We analyzed these 18 ca ses and found that 11 showed evidence of hOGG1 allelic loss. By immunohisto chemical staining on a total of 71 HNSCC cases using a commercially availab le anti-hOGG1 antibody, we showed that hOGG1 gene expression was markedly s uppressed in up to 38% of the cases. The frequent allelic imbalance and sup pression of the hOGG1 gene thus imply that repair for oxidative DNA damages may be relevant in future studies on head and neck squamous carcinogenesis .