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ABSTRACT The tissue inhibitor of metalloproteinases-2 (TIMP-2) is known to antagonize matrix metalloproteinase activity and to suppress tumor growth, angiogenesis, invasion and metastasis.

We analysed the methylation status of the CpG island in the TIMP-2 promoter region by methylation-specific polymerase chain reaction (MSP) in hematopoietic cell lines. TIMP-2 promoter

hypermethylation in the lymphoma cell line Raji and the leukemia cell line KG1a was associated with transcriptional repression. Treatment with the demethylating agent 5-aza-2′-deoxycytidine

resulted in TIMP-2 upregulation in both cell lines. TIMP-2 was expressed in the cell lines HL60, U266 and XG1, which carry an unmethylated promoter region. MSP analysis of primary patient

samples revealed aberrant methylation of TIMP-2 in 33/90 (36.7%) cases of non-Hodgkin's lymphoma (NHL), but not in normal peripheral blood lymphocytes as well as in nonmalignant bone

marrow and lymph nodes. The frequency of TIMP-2 methylation was slightly higher in aggressive NHL subtypes compared to those with an indolent subtype (38.6 versus 33.3%). In contrast, TIMP-2

was not hypermethylated in any of the 40 cases of acute myelogenous leukemia examined. We conclude that promoter hypermethylation of TIMP-2 is a novel epigenetic event in the pathogenesis

of lymphoid malignancies and may contribute to a more aggressive NHL phenotype. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS PROGNOSTIC AND IMMUNE CORRELATION OF IDO1 PROMOTER METHYLATION IN

BREAST CANCER Article Open access 13 November 2024 GENOME-WIDE DNA METHYLATION PATTERNS REVEAL CLINICALLY RELEVANT PREDICTIVE AND PROGNOSTIC SUBTYPES IN HUMAN OSTEOSARCOMA Article Open

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Yoshizaki T, Maruyama Y, Sato H and Furukawa M . (2001). _Int. J. Cancer_, 95, 44–50. Download references ACKNOWLEDGEMENTS We thank S Mellen and L Messler for expert technical assistance.

This work was supported by NIH Grants CA84986 and P50 CA96888 and a grant from the Rheinisch-Westfaelische Technische Hochschule Aachen. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * The

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans St, Baltimore, 21231, MD, USA Oliver Galm, Hiromu Suzuki, Yoshimitsu Akiyama, Manel Esteller, Malcolm V Brock, 

Stephen B Baylin & James G Herman * Medizinische Klinik IV, Universitaetsklinikum Aachen, Aachen, 52074, Germany Oliver Galm & Rainhardt Osieka * Cancer Epigenetics Laboratory,

Spanish National Cancer Centre, Madrid, 28029, Spain Manel Esteller Authors * Oliver Galm View author publications You can also search for this author inPubMed Google Scholar * Hiromu Suzuki

View author publications You can also search for this author inPubMed Google Scholar * Yoshimitsu Akiyama View author publications You can also search for this author inPubMed Google

Scholar * Manel Esteller View author publications You can also search for this author inPubMed Google Scholar * Malcolm V Brock View author publications You can also search for this author

inPubMed Google Scholar * Rainhardt Osieka View author publications You can also search for this author inPubMed Google Scholar * Stephen B Baylin View author publications You can also

search for this author inPubMed Google Scholar * James G Herman View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to

James G Herman. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Galm, O., Suzuki, H., Akiyama, Y. _et al._ Inactivation of the tissue inhibitor of

metalloproteinases-2 gene by promoter hypermethylation in lymphoid malignancies. _Oncogene_ 24, 4799–4805 (2005). https://doi.org/10.1038/sj.onc.1208599 Download citation * Received: 24

September 2004 * Revised: 27 December 2004 * Accepted: 01 February 2005 * Published: 02 May 2005 * Issue Date: 14 July 2005 * DOI: https://doi.org/10.1038/sj.onc.1208599 SHARE THIS ARTICLE

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by the Springer Nature SharedIt content-sharing initiative KEYWORDS * promoter hypermethylation * non-Hodgkin's lymphoma * matrix metalloproteinases * angiogenesis