Diffuse Large B Cell Lymphoma Shows Distinct MethylationProfiles of the Tumor Suppressor Genes among theNon-Hodgkin’s Lymphomas
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Aberrant methylation of CpG islands in promoter regions is one of the major mechanisms for silencing of tumor suppressor genes in various types of human cancers including non-Hodgkin’s lymphomas (NHL). In this study, we investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in NHLs and compared the methylation profiles between B-cell and T/NK-cell NHLs. Methods : 54 cases of B-cell NHLs and 16 cases of T/NK-cell NHLs were examined for the methylation status of eight genes using methylation specific PCR. Results : CpG islands methylation was variously found in eight genes as follows; DAPK (71%), MT1G (70%), p16 (53%), CDH1 (53%), THBS1 (56%), MGMT (27.1%), COX2 (13%), and RUNX3 (11.4%). In six cases (8 %), methylation was not observed in any of these genes. Overall methylation index of B-cell NHLs (0.48) was significantly higher than that of T/NK-cell NHLs (0.32). Of eight genes tested, THBS1 and CDH1 methylations were much more prominent in diffuse large B-cell lymphomas than in T/NK-cell NHLs or other B-cell NHLs. Conclusion : This study suggests that aberrant CpG island methylation is a frequent event in NHLs, and diffuse large B-cell lymphomas show overlapping but distinct methylation profiles.
Abstract
Aberrant methylation of CpG islands in promoter regions is one of the major mechanisms for silencing of tumor suppressor genes in various types of human cancers including non-Hodgkin’s lymphomas (NHL). In this study, we investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in NHLs and compared the methylation profiles between B-cell and T/NK-cell NHLs. Methods : 54 cases of B-cell NHLs and 16 cases of T/NK-cell NHLs were examined for the methylation status of eight genes using methylation specific PCR. Results : CpG islands methylation was variously found in eight genes as follows; DAPK (71%), MT1G (70%), p16 (53%), CDH1 (53%), THBS1 (56%), MGMT (27.1%), COX2 (13%), and RUNX3 (11.4%). In six cases (8 %), methylation was not observed in any of these genes. Overall methylation index of B-cell NHLs (0.48) was significantly higher than that of T/NK-cell NHLs (0.32). Of eight genes tested, THBS1 and CDH1 methylations were much more prominent in diffuse large B-cell lymphomas than in T/NK-cell NHLs or other B-cell NHLs. Conclusion : This study suggests that aberrant CpG island methylation is a frequent event in NHLs, and diffuse large B-cell lymphomas show overlapping but distinct methylation profiles.
참고문헌 (24)
- Jones PA, "The fundamental role of epigenetic events in cancer", Nat Rev Genet, 3, pp.415~428 (2002)
- Costello JF, "Aberrant CpG-island methylation has non-random and tumour-type-specific patterns", Nat Genet, 24, pp.132~138 (2000)
- Esteller M, "CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future", Oncogene, 21, pp.5427~5440 (2002)
- Esteller M, "A gene hypermethylation profile of human cancer", Cancer Res, 61, pp.3225~3229 (2001)
- Baur AS, "Frequent methylation silencing of p15(INK4b) (MTS2) and p16 (INK4a) (MTS1) in B-cell and T-cell lymphomas", Blood, 94, pp.1773~1781 (1999)
- Chu LC, "Epigenetic silencing of multiple genes in primary CNS lymphoma", Int J Cancer, 119, pp.2487~2491 (2006)
- Esteller M, "Hypermethylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma", J Natl Cancer Inst, 94, pp.26~32 (2002)
- Katzenellenbogen RA, "Hypermethylation of the DAP-kinase CpG island is a common alteration in B-cell malignancies", Blood, 93, pp.4347~4353 (1999)
- Rossi D, "Aberrant promoter methylation of multiple genes throughout the clinico-pathologic spectrum of B-cell neoplasia", Haematologica, 89, pp.154~164 (2004)
- Akhtar M, "Promoter methylation regulates Helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells", Cancer Res, 61, pp.2399~2403 (2001)
- Herman JG, "Methylation- specific PCR: a novel PCR assay for methylation status of CpG islands", Proc Natl Acad Sci USA, 93, pp.9821~9826 (1996)
- Kang GH, "Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia", J Pathol, 202, pp.233~240 (2004)
- Ueki T, "Hypermethylation of multiple genes in pancreatic adenocarcinoma", Cancer Res, 60, pp.1835~1839 (2000)
- Morris MR, "Multigene methylation analysis of Wilms’ tumour and adult renal cell carcinoma", Oncogene, 22, pp.6794~6801 (2003)
- Jaffe ES, , pp.351~ (2001)
- Maruyama R, "Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features", Cancer Res, 61, pp.8659~8663 (2001)
- Takahashi T, "DNA methylation profiles of lymphoid and hematopoietic malignancies", Clin Cancer Res, 10, pp.2928~2935 (2004)
- Li Q, "Methylation and silencing of the Thrombospondin-1 promoter in human cancer", Oncogene, 18, pp.3284~3289 (1999)
- Henrique R, "MT1G hypermethylation is associated with higher tumor stage in prostate cancer", Cancer Epidemiol Biomarkers Prev, 14, pp.1274~1278 (2005)
- Huang Y, "Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma", Int J Cancer, 104, pp.735~744 (2003)
- Roth MJ, "p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in esophageal squamous cell carcinoma and its precursor lesions", Oncol Rep, 15, pp.1591~1597 (2006)
- Li QL, "Causal relationship between the loss of RUNX3 expression and gastric cancer", Cell, 109, pp.113~124 (2002)
- Toyota M, "Aberrant methylation of the Cyclooxygenase 2 CpG island in colorectal tumors", Cancer Res, 60, pp.4044~4048 (2000)
- Santini V, "Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications", Ann Intern Med, 134, pp.573~586 (2001)