Expression of human 8-oxoguanine DNA glycosylase (hOGG1) in follicular lymphoma

Abstract

The human homologue of the yeast DNA repair enzyme 8-oxoguanine DNA glycosylase (hOGG1) repairs oxidatively damaged guanosine nucleotides in DNA. This enzyme is highly expressed in reactive germinal centers, where lymphoid cells are under oxidative stress, and has been thought to protect lymphocytes from mutation. As a first step to investigate the role of hOGG1 in lymphomagenesis, we evaluated hOGG1 expression in follicular lymphoma. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue of 28 follicular lymphoma cases (16 grade 1, seven grade 2, and five grade 3) to evaluate the expression of hOGG1 in neoplastic follicles. Reactive germinal centers of non-neoplastic tonsil and lymph node tissue were also examined. Fluorescent-in-situ hybridization (FISH) was performed using a DNA probe from BAC clone RP11-266J6 corresponding to 3p25, where the hOGG1 gene resides, to evaluate for the presence or absence of a deletion. In reactive germinal centers, the majority of centroblasts and centrocytes were positive for hOGG1. In contrast, the majority (21 of 28 or 75%) of follicular lymphoma cases showed absent/minimal expression of hOGG1. Only four of 28 (14%) follicular lymphoma cases revealed the same levels of hOGG1 expression as reactive germinal centers. There was no correlation between hOGG1 expression and histologic grade. None of the 16 cases evaluated by FISH showed a deletion of hOGG1. Furthermore, absent/minimal hOGG1 expression was observed in four of six Bcl-2-negative follicular lymphoma cases. Our findings suggest that absent/minimal hOGG1 expression occurs in the majority of follicular lymphomas. The downregulation of hOGG1 does not appear to be due to a deletion of the hOGG1 locus. Additionally, finding absent/minimal hOGG1 expression in a subset of Bcl-2-negative follicular lymphomas suggests that hOGG1 may have utility in diagnosing Bcl-2-negative follicular lymphomas. Keywords: follicular lymphoma; hOGG1; immunohistochemistry The human homologue of the yeast DNA repair enzyme, 8-oxoguanine-DNA glycosylase (hOGG1), excises 8-oxoguanine, an oxidative form of the guanine nucleotide. 1 HOGG1 shares a 38% identity with the yeast OGG1. It has been localized to chromosome 3p25 by fluorescent-in-situ hybridization (FISH) by Radicella et al in 1997, 2 and it was cloned by Rosenquist et al 3 in 1997. This DNA glycosylase/apurinic lyase repairs oxidative DNA damage, specifically 8-oxoguanine/C base pairs. 8-hydroxyguanine is highly mutagenic via GC to TA transversions 4 and is generated by oxidative stresses as well as normal cellular metabolism. 5 It is believed that hOGG1's role of excising 8-oxoguanine protects DNA against the mutagenic effects of oxidative damage and decreased cell survival from radiation-induced damage. 6 Supporting hOGG1's role of hindering mutagenesis is that certain a genetic polymorphism of hOGG1, Ser326Cys, has been implicated in an increased incidence of adenocarcinoma of the lung 7 and squamous cell carcinoma of the lung 8,9 in patients with the Cys/Cys genoty...

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“…Human 8‐oxoguanine‐DNA glycosylase 1 (hOGG1) is the main enzyme that excises 8‐oxo‐dG from damaged DNA via the base‐excision repair pathway [9]. It was suggested that cells under oxidative stress may require increased expression of hOGG1 to protect them from oxidative damage‐induced mutations [10].…”

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