[1496] Differential CpG Methylation Profile of the ID4, GADD45G and DAPK Genes in Marginal Zone Lymphomas and Diffuse Large B Cell Lymphomas

Kathryn A Rizzo, Zijin Zhao, Jianjun Zhang, Mehdi Nassiri. Indiana University School of Medicine, Indianapolis, IN; University of South Carolina School of Medicine, Professional Pathology Services, Columbia, SC

Background: Epigenetic regulation via CpG methylation of tumor suppressor genes affects signaling pathways involved in lymphomagenesis and may give insight into targeted therapies. We undertook a study to evaluate the differential methylation pattern of genes implicated in oncogenesis. The id4 gene is necessary for lymphocyte development. GADD45G is a stress response gene which activates the p38/c-Jun pathway. The DAPK gene has been implicated in gastric and cutaneous marginal zone lymphomas. The methylation status of these genes were evaluated in benign lymphoid tissue, marginal zone lymphomas (MZL), and diffuse large B cell lymphomas (DLBCL).
Design: 77 cases were evaluated including 25 benign lymphoid cases, 31 MZL and 21 DLBCL. MZL cases included extranodal, nodal and splenic MZL and DLBCL cases were composed of de novo and two cases of secondary DLBCL from MZL. The methylation status of GADD45G, DAPK and ID4 genes were determined using MS-PCR. Each pair of primers were designed for the methylated and unmethylated alleles of each gene and primers for the internal control, β-actin were used. PCR products were analyzed and the methylation frequencies of each gene were evaluated between the three groups using the Fisher's Exact Test.
Results:

Table 1. Differential Methylation Frequency
GeneDiffuse large B-cell lymphomaMarginal zone lymphomaBenign
ID480.95% (17/21)41.94% (13/31)24% (6/25 )
GADD45G42.86% (9/21)35.48% (11/31)16% (4/25 )
DAPK77.78% (14/18)64.52% (20/31)24% (6/25 )




Table 2. Significance of Methylation Pattern for MZL and DLBCL
GeneDLBCL vs. MZLDLBCL vs. BenignMZL vs. Benign
ID40.00930.00030.2560
GADD45G0.77210.05590.1345
DAPK0.52130.00070.0033



Conclusions: Distinct methylation profiles are seen in the ID4 and DAPK genes between benign, MZL, and DLBCL cases. The ID4 gene demonstrates a statistically significant increase in methylation in lymphoma cases versus benign and in ABL compared to MZL. Increased DAPK methylation was seen in the two lymphoma subgroups compared to benign tissue. GADD45 methylation showed no significant difference between the three groups. The differential methylation profile provides insights into the development of lymphomagenesis via epigenetic regulation of indolent and aggressive lymphomas.
Category: Hematopathology

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 257, Tuesday Afternoon

 

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