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Short Report
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
Jianming Ying, Hongyu Li, Paul Murray, Zifen Gao, Yun-Wen Chen, Yajun Wang, Kwan Yeung Lee, Anthony T.C. Chan, Richard F. Ambinder, Gopesh Srivastava and Qian Tao
volume 2 | issue 1
january/february/march 2007Pages: 15 - 21
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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.
Authors
Jianming Ying
Chinese University of Hong Kong, Hong Kong
Hongyu Li
Chinese University of Hong Kong, Hong Kong
Paul Murray
University of Birmingham, UK
Zifen Gao
Peking University Health Science Center, Beijing, China
Yun-Wen Chen
University of Hong Kong, Hong Kong China
Yajun Wang
Chinese University of Hong Kong, Hong Kong
Kwan Yeung Lee
Chinese University of Hong Kong, Hong Kong
Anthony T.C. Chan
Chinese University of Hong Kong, Hong Kong
Richard F. Ambinder
Johns Hopkins School of Medicine, Baltimore, MD
Gopesh Srivastava
University of Hong Kong, Hong Kong China
Qian Tao
University of Hong Kong
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.