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.
|Gene||Diffuse large B-cell lymphoma||Marginal zone lymphoma||Benign|
|ID4||80.95% (17/21)||41.94% (13/31)||24% (6/25 )|
|GADD45G||42.86% (9/21)||35.48% (11/31)||16% (4/25 )|
|DAPK||77.78% (14/18)||64.52% (20/31)||24% (6/25 )|
|Gene||DLBCL vs. MZL||DLBCL vs. Benign||MZL vs. Benign|