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学科主题: 基础医学
题名:
Epigenetic Silencing of a Proapoptotic Cell Adhesion Molecule, the Immunoglobulin Superfamily Member IGSF4, by Promoter CpG Methylation Protects Hodgkin Lymphoma Cells from Apoptosis
作者: 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
发表日期: 2010-09-01
DOI: 10.2353/ajpath.2010.100052
卷: 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
项目资助者: Leukemia Research Fund UK ; Cancer Research UK ; Johns Hopkins Singapore ; Chinese University of Hong Kong
WOS记录号: WOS:000281717700042
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50968
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.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

Recommended Citation:
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.
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