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Prognostic significance of O6-methylguanine DNA methyltransferase and p57 methylation in patients with diffuse large B-cell lymphomas

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Abstract:

Lee SM, Lee EJ, Ko Y-H, Lee SH, Maeng L, Kim K-M. Prognostic significance of O6-methylguanine DNA methyltransferase and p57 methylation in patients with diffuse large B-cell lymphomas. APMIS 2009; 117: 87–94.

To evaluate whether promoter methylation is related to responsiveness for chemotherapy or clinical outcome, we performed an association analysis between methylation and clinical outcomes. Patients with nodal diffuse large B-cell lymphomas (DLBCL) at a single institute (n=44) were studied for methylation of tumor-related genes, MGMT, p15INK4B, p16INK4A, p16INK4A, Mad2, TMS1/ASC, CASP8, and GSTP1. The clinical behavior of DLBCL after chemotherapy was followed up and analyzed. Hypermethylation of promoters of MGMT, p15INK4B, p16INK4A, p16INK4A, Mad2, and TMS1/ASC genes was observed in 52.3%, 31.8%, 54.5%, 47.7%, 50%, and 2.3% of the cases, respectively. Methylation of CASP8 and GSTP1 genes was not observed. Promoter methylation was not related to chemo-responsiveness, disease-free survival, and progress of disease after chemotherapy. However, in overall survival analyses, MGMT methylation (p<0.05) and responsiveness to chemotherapy (p<0.01) were significant prognostic factors in patients with DLBCL. In the low-risk group, patients with p57 methylation showed longer overall survival than patients without p57 methylation (p=0.02) and all patients with p57 methylation were alive during follow-up. Our results demonstrate that aberrant promoter methylation of MGMT and p57 is an additional biological marker for predicting increased overall survival in patients with DLBCL.

Keywords: B-cell; Lymphomas; MGMT; methylation; p57; prognosis

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2008.00017.x

Affiliations: 1: Department of Pathology, The Catholic University of Korea, Seoul; and 2: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Publication date: February 1, 2009

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