Possible role of GADD45? methylation in diffuse large B-cell Lymphoma: Does it affect the progression and tissue involvement?

Abstract

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45?) is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45? methylation, to evaluate the correlation between GADD45? methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. Materials and Methods: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45? methylation status. The GADD45? protein expression was determined by immunohistochemistry. Results: GADD45? methylation was frequent (50.0%) in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041). In contrast, unmethylated GADD45? was associated with nodal involvement as the primary anatomical site (p=0.040). Conclusion: The results of this study show that, in contrast to solid tumors, the frequency of GADD45? methylation is higher and this epigenetic alteration of GADD45? may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45?. © 2015 Turkish Society of Hematology. All rights reserved.