Correlation between promoter hypermethylation of GSTP1 and response to chemotherapy in diffuse large B cell lymphoma.
Glutathione-S-transferase P1 (GSTP1) and O6-methylguanine DNA methyltransferase (MGMT) are involved in drug-resistant to chemotherapeutic agents such as doxorubicin. In this study, prognostic significance of promoter hypermethylation and mRNA and protein expression of GSTP1 and MGMT together with promoter hypermethylation of death-associated protein kinase (DAPK) in diffuse large B cell lymphoma (DLBCL) was analyzed. Fifty-three patients with DLBCL, 24 men and 29 women, with age ranging from 23 to 91 (median 65), were analyzed. Genomic DNA and total RNA extracted from frozen samples of DLBCL were analyzed by methylation-specific polymerase chain reaction and quantitative reverse transcription polymerase chain reaction (RT-PCR) to determine promoter hypermethylation and mRNA expression of GSTP1, MGMT, and DAPK. Immunohistochemical analysis was performed to determine GSTP1 and MGMT expression at the protein level. Promoter hypermethylation of GSTP1, MGMT, and DAPK was detected in 12 (22.6%), 21 (39.6%), and 36 (67.9%) of 53 patients, respectively. Quantitative RT-PCR and immunohistochemistry did not show a correlation between methylation status and mRNA and protein expression of GSTP1 and MGMT. Patients with GSTP1 promoter hypermethylation showed a better 5-year overall survival rate than those without (100 vs 62.2%; p < 0.05). However, GSTP1 promoter hypermethylation was not an independent prognosticator in multivariate analysis. Methylation status of GSTP1 could be an indicator of drug response and a prognosticator for DLBCL.
Nakamichi
Itsuko
I
Department of Pathology (C3), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tomita
Yasuhiko
Y
Zhang
Binglin
B
Sugiyama
Haruo
H
Kanakura
Yuzuru
Y
Fukuhara
Shirou
S
Hino
Masayuki
M
Kanamaru
Akihisa
A
Ogawa
Hiroyasu
H
Aozasa
Katsuyuki
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D064550:Death-Associated Protein Kinases; D005260:Female; D005500:Follow-Up Studies; D020868:Gene Silencing; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045643:DNA Repair Enzymes