Frequent allelic loss at chromosome 3p distinct from genetic alterations of the 8-oxoguanine DNA glycosylase 1 gene in head and neck cancer

Abstract

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.

Frequent Allelic Imbalance and Loss of Protein Expression of the DNA Repair Gene hOGG1 in Head and Neck Squamous Cell Carcinoma

“…The frequency (61.1%) of the hOGG1 allelic loss in HNSCC in this study is similar to that (55%) obtained by Blons et al (1999) using five microsatellite markers. Allelic loss in our study affected both polymorphic alleles with equal frequency (Table 2).…”

“…In a report by Blons et al (1999), the investigators failed to find any identifiable mutations in the hOGG1 gene-coding sequence in HNSCC cases with evidence of hOGG1 allelic loss. This result, in combination with those by others (Chevillard et al, 1998;Kohno et al, 1998;Shinmura et al, 1998), indicates that somatic mutations of the hOGG1 gene appear to be very rare events in tumors of the upper aerodigestive tract and that promoter hypermethylation should be explored as a possible epigenetic mechanism for gene inactivation.…”

hOGG1 Ser326Cys polymorphism and G:C‐to‐T:A mutations: No evidence for a role in tobacco‐related non small cell lung cancer

“…24 The site of the hOGG1 gene is frequently deleted in lung and other tobacco-related neoplasms, suggesting other critical genes in close proximity to hOGG1. 28,49 The codon 326 polymorphism may be in linkage disequilibrium with other functional polymorphisms in cancerrelated genes on chromosome 3p. 50 In summary, the hOGG1 codon 326 Ser/Ser genotype was associated with an increase in p53 mutations in tobacco-related NSCLC.…”

Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma

“…Indeed p16 on 9p21 and TP53 on 17p21 demonstrated either promoter hypermethylation or mutations as a second hit of inactivation (Cabelguenne et al, 2000;ElNaggar et al, 1997). Concerning chromosome 3p, several genes have been suspected and studied as TGFbRII (Garrigue-Antar et al, 1995), OGG1 (Blons et al, 1999b), and FHIT (Kisielewski et al, 1998;Mao et al, 1996) but their roles are still not ascertained. TSG implicated in HNSCC carcinogenesis and located on chromosomes 8p and 18q remain to be identified.…”