IR@PKUHSC  > 北京大学基础医学院  > 病理学系
学科主题基础医学
Epigenetic Silencing of a Proapoptotic Cell Adhesion Molecule, the Immunoglobulin Superfamily Member IGSF4, by Promoter CpG Methylation Protects Hodgkin Lymphoma Cells from Apoptosis
Murray, Paul G.1; Fan, Yichao1; Davies, Gillian1; Ying, Jianming4,5; Geng, Hua1; Ng, Ka Man1; Li, Hongyu4; Gao, Zifen1; Wei, Wenbin1; Bose, Shikha1; Anderton, Jennifer1; Kapatai, Georgia1; Reynolds, Gary1; Ito, Akihiko8; Marafioti, Teresa9; Woodman, Ciaran B. J.1; Ambinder, Richard10; Tao, Qian2,4,10
刊名AMERICAN JOURNAL OF PATHOLOGY
2010-09-01
DOI10.2353/ajpath.2010.100052
177期:3页:1480-1490
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pathology
研究领域[WOS]Pathology
关键词[WOS]TUMOR-SUPPRESSOR GENE ; REED-STERNBERG CELLS ; LUNG-CANCER ; HEPATOCELLULAR CARCINOGENESIS ; COLORECTAL-CANCER ; B-CELLS ; TSLC1 ; HYPERMETHYLATION ; CARCINOMAS ; EXPRESSION
英文摘要

The malignant Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) are believed to derive from germinal center (GC) B cells, but lack expression of a functional B cell receptor. As apoptosis is the normal fate of B-cell receptor negative GC B cells, mechanisms that abrogate apoptosis are thus critical in HL development, such as epigenetic disruption of certain pro-apoptotic cancer genes including tumor suppressor genes. Identifying methylated genes elucidates oncogenic mechanisms and provides valuable biomarkers; therefore, we performed a chemical epigenetic screening for methylated genes in HI. through pharmacological demethylation and expression profiling. IGST4/CADM1/TSLC1, a pro-apoptotic cell adhesion molecule of the immunoglobulin superfamily, was identified together with other methylated targets. In contrast to its expression in normal GC B cells, IGSF4 was down-regulated and methylated in cell lines, most primary HL, and microdissected HRS cells of 3/5 cases, but not in normal peripheral blood mononuclear cells and seldom in normal lymph nodes. We also detected IGSF4 methylation in sera of 14/18 (78%) HL patients but seldom in normal sera. Ectopic IGSF4 expression decreased HL cells survival and increased their sensitivity to apoptosis. IGSF4 induction that normally follows heat shock stress treatment was also abrogated in methylated lymphoma cells. Thus, our data demonstrate that IGSF4 silencing by CpG methylation provides an anti-apoptotic signal to HRS cells important in HL pathogenesis. (Am J Pathol 2010. 177:1480-1490; 10.2353/ajpath.2010.100052)

语种英语
WOS记录号WOS:000281717700042
资助机构Leukemia Research Fund UK ; Cancer Research UK ; Johns Hopkins Singapore ; Chinese University of Hong Kong
引用统计
被引频次:16[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50968
专题北京大学基础医学院_病理学系
作者单位1.John Hopkins Singapore, Singapore, Singapore
2.Kobe Univ, Div Surg Pathol, Grad Sch Med, Kobe, Hyogo 657, Japan
3.UCL, Dept Pathol, London, England
4.Univ Birmingham, Canc Res UK Inst Canc Studies, Birmingham, W Midlands, England
5.Chinese Univ Hong Kong, Ctr Canc, Dept Clin Oncol, PWH,Hong Kong Canc Inst, Hong Kong, Hong Kong, Peoples R China
6.Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China
7.Chinese Acad Med Sci, Dept Pathol, Canc Hosp, Beijing 100037, Peoples R China
8.Chinese Acad Med Sci, Inst Canc, Peking Union Med Coll, Beijing 100037, Peoples R China
9.Peking Univ, Dept Pathol, Hlth Sci Ctr, Beijing 100871, Peoples R China
10.Johns Hopkins Sch Med, Sydney Kimmel Comprehens Canc Ctr, Baltimore, MD USA
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Murray, Paul G.,Fan, Yichao,Davies, Gillian,et al. Epigenetic Silencing of a Proapoptotic Cell Adhesion Molecule, the Immunoglobulin Superfamily Member IGSF4, by Promoter CpG Methylation Protects Hodgkin Lymphoma Cells from Apoptosis[J]. AMERICAN JOURNAL OF PATHOLOGY,2010,177(3):1480-1490.
APA Murray, Paul G..,Fan, Yichao.,Davies, Gillian.,Ying, Jianming.,Geng, Hua.,...&Tao, Qian.(2010).Epigenetic Silencing of a Proapoptotic Cell Adhesion Molecule, the Immunoglobulin Superfamily Member IGSF4, by Promoter CpG Methylation Protects Hodgkin Lymphoma Cells from Apoptosis.AMERICAN JOURNAL OF PATHOLOGY,177(3),1480-1490.
MLA Murray, Paul G.,et al."Epigenetic Silencing of a Proapoptotic Cell Adhesion Molecule, the Immunoglobulin Superfamily Member IGSF4, by Promoter CpG Methylation Protects Hodgkin Lymphoma Cells from Apoptosis".AMERICAN JOURNAL OF PATHOLOGY 177.3(2010):1480-1490.
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