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学科主题: 基础医学
题名:
Tumor-specific methylation of the 8p22 tumor suppressor gene DLC1 is an epigenetic biomarker for Hodgkin, nasal NK/T-cell and other types of lymphomas
作者: Ying, Jianming2,3; Li, Hongyu2,3; Murray, Paul4; Gao, Zifen5; Chen, Yun-Wen1; Wang, Yajun2,3; Lee, Kwan Yeung2,3; Chan, Anthony T. C.2,3; Ambinder, Richard F.; Srivastava, Gopesh1; Tao, Qian2,3,6
关键词: DLC1 ; methylation ; biomarker ; lymphoma ; tumor suppressor gene
刊名: EPIGENETICS
发表日期: 2007
卷: 2, 期:1, 页:15-21
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: EPSTEIN-BARR-VIRUS ; ABERRANT DNA METHYLATION ; STRESS-RESPONSIVE GENE ; HUMAN BREAST-CANCER ; PROMOTER HYPERMETHYLATION ; HEMATOPOIETIC MALIGNANCIES ; HEPATOCELLULAR-CARCINOMA ; NASOPHARYNGEAL CARCINOMA ; FUNDAMENTAL ROLE ; SERUM DNA
英文摘要:

Aberrant promoter methylation is an epigenetic mechanism for silencing tumor suppressor genes (TSG), and is also a biomarker for early cancer diagnosis and prognosis prediction. Recently, we and others identified DLC1 (ARHGAP7) as a functional TSG frequently methylated in multiple carcinomas. Here, we further uncovered DLC1 as one of the up-regulated genes in lymphoma cell lines after pharmacologic demethylation with 5-aza-2 ′-deoxycytidine (Aza). Transcriptional silencing and methylation of DLC1 was detected in most Hodgkin (HL) and non-Hodgkin lymphoma (NHL) cell lines, including 4/6 Hodgkin, 4/4 nasal NK/T-cell, 6/6 Burkitt and 5/5 diffuse large B-cell lymphoma cell lines. Aza treatment led to DLC1 promoter demethylation and transcriptional reactivation in silenced cell lines, indicating a methylation-mediated silencing. Aberrant methylation was further detected in 44% (14/37) Hodgkin, 77% (34/44) nasal NK/T-cell and 60-90% of various types of primary NHLs, but not in any normal lymph node or PBMC sample, and is thus tumor-specific. Analysis of microdissected Hodgkin/Reed-Sternberg (HRS) cells from HL cases confirmed the site of methylation as tumor cells. Moreover, DLC1 methylation was detected in 4/14 (29%) serum samples from HL patients. Our results indicate that DLC1 methylation is a frequent event in multiple lymphomagenesis and could serve as a tumor-specific biomarker for future lymphoma diagnosis.

语种: 英语
WOS记录号: WOS:000256223000005
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67810
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
2.Chinese Univ Hong Kong, Hong Kong Canc Inst, Dept Clin Oncol,Canc Epigenet Lab, Sir YK Pao Ctr Canc,State Key Lab Oncol S China, Hong Kong, Hong Kong, Peoples R China
3.Chinese Univ Hong Kong, Li Ka Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China
4.Univ Birmingham, Canc Res UK Inst Canc Studies, Birmingham, W Midlands, England
5.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100871, Peoples R China
6.Johns Hopkins Sch Med, Johns Hopkins Singapore & Sidney Kimmel Comprehen, Baltimore, MD USA

Recommended Citation:
Ying, Jianming,Li, Hongyu,Murray, Paul,et al. Tumor-specific methylation of the 8p22 tumor suppressor gene DLC1 is an epigenetic biomarker for Hodgkin, nasal NK/T-cell and other types of lymphomas[J]. EPIGENETICS,2007,2(1):15-21.
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