title: Prognostic significance of O6-methylguanine DNA methyltransferase and p57 methylation in patients with diffuse large B-cell lymphomas.
abstract: 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, p15(INK4B), p16(INK4A), p16(INK4A), Mad2, TMS1/ASC, CASP8, and GSTP1. The clinical behavior of DLBCL after chemotherapy was followed up and analyzed. Hypermethylation of promoters of MGMT, p15(INK4B), p16(INK4A), p16(INK4A), 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.
authors.affiliation: Department of Pathology, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Lee
authors.forename: Eui Jin
authors.initials: EJ
authors.lastname: Lee
authors.forename: Young-Hyeh
authors.initials: YH
authors.lastname: Ko
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Leeso
authors.initials: L
authors.lastname: Maeng
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018899:CpG Islands; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics*; D019175:DNA Methylation; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D019853:O(6)-Methylguanine-DNA Methyltransferase