|Epigenetic silencing of the 3p22 tumor suppressor DLEC1 by promoter CpG methylation in non-Hodgkin and Hodgkin lymphomas|
|Wang, Zhaohui1,2; Li, Lili1,2; Su, Xianwei2; Gao, Zifen3; Srivastava, Gopesh4; Murray, Paul G.5; Ambinder, Richard6,7; Tao, Qian1,2,6,7|
|关键词||DLEC1 CpG Methylation Tumor suppressor Lymphoma|
|刊名||JOURNAL OF TRANSLATIONAL MEDICINE|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, Research & Experimental|
|研究领域[WOS]||Research & Experimental Medicine|
|关键词[WOS]||HUMAN-CHROMOSOME 3P21.3 ; HOMOZYGOUS DELETION REGION ; NASOPHARYNGEAL CARCINOMA ; LUNG-CANCER ; CLINICOPATHOLOGICAL SIGNIFICANCE ; ABERRANT METHYLATION ; DNA METHYLATION ; UTERINE CERVIX ; CELL CARCINOMA ; HIGH-FREQUENCY|
Background: Inactivaion of tumor suppressor genes (TSGs) by promoter CpG methylation frequently occurs in tumorigenesis, even in the early stages, contributing to the initiation and progression of human cancers. Deleted in lung and esophageal cancer 1 (DLEC1), located at the 3p22-21.3 TSG cluster, has been identified frequently silenced by promoter CpG methylation in multiple carcinomas, however, no study has been performed for lymphomas yet.
Methods: We examined the expression of DLEC1 by semi-quantitative reverse transcription (RT)-PCR, and evaluated the promoter methylation of DLEC1 by methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) in common lymphoma cell lines and tumors.
Results: Here we report that DLEC1 is readily expressed in normal lymphoid tissues including lymph nodes and PBMCs, but reduced or silenced in 70% (16/23) of non-Hodgkin and Hodgkin lymphoma cell lines, including 2/6 diffuse large B-cell (DLBCL), 1/2 peripheral T cell lymphomas, 5/5 Burkitt, 6/7 Hodgkin and 2/3 nasal killer (NK)/T-cell lymphoma cell lines. Promoter CpG methylation was frequently detected in 80% (20/25) of lymphoma cell lines and correlated with DLEC1 downregulation/silencing. Pharmacologic demethylation reversed DLEC1 expression in lymphoma cell lines along with concomitant promoter demethylation. DLEC1 methylation was also frequently detected in 32 out of 58 (55%) different types of lymphoma tissues, but not in normal lymph nodes. Furthermore, DLEC1 was specifically methylated in the sera of 3/13 (23%) Hodgkin lymphoma patients.
Conclusions: Thus, methylation-mediated silencing of DLEC1 plays an important role in multiple lymphomagenesis, and may serve as a non-invasive tumor marker for lymphoma diagnosis.
|项目编号||81071634 ; 81172582 ; JC201005270328A|
|资助机构||National Natural Science Foundation of China ; Shenzhen Science Fund for Distinguished Young Scholars ; Leukaemia Lymphoma Research of the United Kingdom ; Chinese University of Hong Kong|
|作者单位||1.Chinese Acad Sci, CUHK, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China|
2.Chinese Univ Hong Kong, Sir YK Pao Ctr Canc, State Key Lab Oncol S China, Canc Epigenet Lab,Dept Clin Oncol, Shatin, Hong Kong, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100871, Peoples R China
4.Univ Hong Kong, Dept Pathol, Shatin, Hong Kong, Peoples R China
5.Univ Birmingham, Canc Res UK Inst Canc Studies, Birmingham, W Midlands, England
6.Johns Hopkins Singapore, Baltimore, MD USA
7.Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA
|Wang, Zhaohui,Li, Lili,Su, Xianwei,et al. Epigenetic silencing of the 3p22 tumor suppressor DLEC1 by promoter CpG methylation in non-Hodgkin and Hodgkin lymphomas[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2012,10(1).|
|APA||Wang, Zhaohui.,Li, Lili.,Su, Xianwei.,Gao, Zifen.,Srivastava, Gopesh.,...&Tao, Qian.(2012).Epigenetic silencing of the 3p22 tumor suppressor DLEC1 by promoter CpG methylation in non-Hodgkin and Hodgkin lymphomas.JOURNAL OF TRANSLATIONAL MEDICINE,10(1).|
|MLA||Wang, Zhaohui,et al."Epigenetic silencing of the 3p22 tumor suppressor DLEC1 by promoter CpG methylation in non-Hodgkin and Hodgkin lymphomas".JOURNAL OF TRANSLATIONAL MEDICINE 10.1(2012).|
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