Association between lymphoma prognosis and aberrant methylation of ID4 and ZO-1 in bone marrow and paraffin-embedded lymphoma tissues of treatment-naive patients

Cen,Jian; Shen,Jianliang; Wang,Xinrong; Kang,Huiyuan; Wang,Lili; Sun,Lu; Li,Yonghui; Yu,Li

doi:10.3892/or.2013.2450

July 2013 Volume 30 Issue 1

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July 2013 Volume 30 Issue 1

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Article

Association between lymphoma prognosis and aberrant methylation of ID4 and ZO-1 in bone marrow and paraffin-embedded lymphoma tissues of treatment-naive patients

Authors:
- Jian Cen
- Jianliang Shen
- Xinrong Wang
- Huiyuan Kang
- Lili Wang
- Lu Sun
- Yonghui Li
- Li Yu
View Affiliations / Copyright

Affiliations: Department of Hematology, Navy General Hospital, Beijing 100048, P.R. China, Department of Hematology, PLA General Hospital, Beijing 1000853, P.R. China
Pages: 455-461
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Published online on: May 10, 2013

https://doi.org/10.3892/or.2013.2450
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Abstract

The aim of the present study was to investigate the association between lymphoma prognosis and aberrant methylation of inhibitor of DNA binding factor 4 (ID4) and tight junction protein 1 (ZO-1) genes in samples isolated from the bone marrow and paraffin-embedded lymphoma tissues of treatment-naive lymphoma patients. The bone marrow biopsy and paraffin-embedded lymphoma tissue samples from treatment-naive lymphoma patients were obtained, along with corresponding control samples from subjects without lymphoma and from lymph nodes of chronic cholecystitis and reactive lymphadenitis patients. Methylation-specific PCR (MSP) reactions were performed to analyze the methylation status on the promoter regions of ID4 and ZO-1. ID4 and ZO-1 promoter regions in the control group were completely unmethylated, whereas the rates of methylation of ID4 and ZO-1 in paraffin-embedded lymphoma tissues of the lymphoma patients were 80.4 and 84.3%, respectively. The methylation positivity rates of both the ID4 or ZO-1 genes in lymphoma patients were 92.2%, which was significantly higher compared to the rates in the control group (0%). The methylation positivity rates of the ID4 and ZO-1 genes in the bone marrow and paraffin-embedded lymphoma tissues of non-Hodgkin lymphoma patients were significantly higher compared to the rates in the Hodgkin lymphoma patients. The survival rate of lymphoma patients with methylated ID4 was significantly lower compared to that of patients with unmethylated ID4. The methylation of the ID4 and ZO-1 genes may be a specific molecular marker for lymphoma diagnosis. The methylation of the ID4 gene may be an indicator of poor prognosis in lymphoma patients.

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1	Kuang SQ, Bai H, Fang ZH, et al: Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia. Blood. 115:2412–2419. 2010. View Article : Google Scholar : PubMed/NCBI
2	Whitman SP, Hackanson B, Liyanarachchi S, et al: DNA hypermethylation and epigenetic silencing of the tumor suppressor gene, SLC5A8, in acute myeloid leukemia with the MLL partial tandem duplication. Blood. 112:2013–2016. 2008. View Article : Google Scholar : PubMed/NCBI
3	Hammond NL and Jahoda CA: Id2, Id3, and Id4 proteins show dynamic changes in expression during vibrissae follicle development. Dev Dyn. 237:1653–1661. 2008. View Article : Google Scholar : PubMed/NCBI
4	Yu L, Liu C, Vandeusen J, et al: Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nat Genet. 37:265–274. 2005. View Article : Google Scholar : PubMed/NCBI
5	Laing JG, Koval M and Steinberg TH: Association with ZO-1 correlates with plasma membrane partitioning in truncated connexin45 mutants. J Membr Biol. 207:45–53. 2005. View Article : Google Scholar : PubMed/NCBI
6	Hoover KB, Liao SY and Bryant PJ: Loss of the tight junction MAGUK ZO-1 in breast cancer: relationship to glandular differentiation and loss of heterozygosity. Am J Pathol. 153:1767–1773. 1998. View Article : Google Scholar : PubMed/NCBI
7	Wang C, Tan Y, Wang G, et al: Study on the relationship between ZO-1 gene expression and the methylation regulation in acute leukemia. Shandong Med J. 32:0022007.(In Chinese).
8	Zhao Y, Wang QS, Li HH, et al: Significance of ID4 promoter methylation in monitoring AML patients with complete remission. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 16:476–478. 2008.(In Chinese).
9	Butler TM and Fletcher GL: Promoter analysis of a growth hormone transgene in Atlantic salmon. Theriogenology. 72:62–71. 2009. View Article : Google Scholar : PubMed/NCBI
10	Papageorgio C, Harrison R, Rahmatpanah FB, Taylor K, Davis W and Caldwell CW: Algorithmic discovery of methylation ‘hot spots’ in DNA from lymphoma patients. Cancer Inform. 6:449–453. 2008.PubMed/NCBI
11	Noetzel E, Veeck J, Niederacher D, et al: Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer. BMC Cancer. 8:1542008. View Article : Google Scholar : PubMed/NCBI
12	Herman JG, Graff JR, Myöhänen S, Nelkin BD and Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 93:9821–9826. 1996. View Article : Google Scholar : PubMed/NCBI
13	Esteller M: Epigenetics in cancer. N Engl J Med. 358:1148–1159. 2008. View Article : Google Scholar
14	Krug U, Ganser A and Koeffler HP: Tumor suppressor genes in normal and malignant hematopoiesis. Oncogene. 21:3475–3495. 2002. View Article : Google Scholar : PubMed/NCBI
15	Miyamoto K and Ushijima T: Diagnostic and therapeutic applications of epigenetics. Jpn J Clin Oncol. 35:293–301. 2005. View Article : Google Scholar : PubMed/NCBI
16	Paz-Carreira J, Garcia-Rivero A, Losada R, et al: Prognostic significance of promoter methylation of multiple genes in germinal center hyperplasia (GCH) and lymphomas of germinal center origin. Blood. 135:114–122. 2009.
17	Delgado J: Novel epigenetic targets in lymphoproliferative disorders. Curr Cancer Drug Targets. 8:378–391. 2008. View Article : Google Scholar : PubMed/NCBI
18	Murray PG, Fan Y, Davies 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. Am J Pathol. 177:1480–1490. 2010. View Article : Google Scholar
19	Amara K, Trimeche M, Ziadi S, Laatiri A, Hachana M and Korbi S: Prognostic significance of aberrant promoter hypermethylation of CpG islands in patients with diffuse large B-cell lymphomas. Ann Oncol. 19:1774–1786. 2008. View Article : Google Scholar : PubMed/NCBI
20	Eberth S, Schneider B, Rosenwald A, et al: Epigenetic regulation of CD44 in Hodgkin and non-Hodgkin lymphoma. BMC Cancer. 10:5172010. View Article : Google Scholar : PubMed/NCBI
21	Conway K, Edmiston SN, Khondker ZS, et al: DNA-methylation profiling distinguishes malignant melanomas from benign nevi. Pigment Cell Melanoma Res. 24:352–360. 2011. View Article : Google Scholar : PubMed/NCBI
22	Carey JP, Asirvatham AJ, Galm O, Ghogomu TA and Chaudhary J: Inhibitor of differentiation 4 (Id4) is a potential tumor suppressor in prostate cancer. BMC Cancer. 9:1732009. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Association between lymphoma prognosis and aberrant methylation of ID4 and ZO-1 in bone marrow and paraffin-embedded lymphoma tissues of treatment-naive patients

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