Imperial College London
Alternate

DrNeloferSyed

Faculty of Medicine, Department of Brain Sciences

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 5292n.syed

 
 
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Location

 

E506Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bower:2009,
author = {Bower, M and Syed, N and Papoudou-Bai, A and Stebbing, J and Naresh, K and Hatzimichael, E and Powles, S and Crook, T},
journal = {J Clin Oncol},
title = {Methylation reversal in high-grade B lymphoma cell lines and novel epigenetic changes conserved between immunocompetent and HIV-positive hosts.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/27962294},
volume = {27},
year = {2009}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 8585 Background: Methylation-dependent transcriptional silencing is an important mechanism of tumour suppressor gene inactivation in neoplasia, including lymphoma. METHODS: Pharmacological "unmasking" of transcriptionally silenced genes in B lymphoma cell lines was achieved using 5' deazacytidine ± Trichostatin A and subsequent analysis of mRNA levels on micro-array. Candidate genes thus identified, were further analysed by qPCR, methylation-specific PCR (MSP) and bisulphite sequencing in B lymphoma cell lines and by MSP in clinical samples from sporadic (immunocompetent) (18 cases) and HIV-infected patients (14 cases). Samples in both patient groups were diffuse large B cell lymphoma (DLBCL) and Burkitt's lymphoma (BL). Additionally, we analysed 8 cases of marginal zone lymphoma (MZL) from the immunocompetent group. RESULTS: We report the identification of 13 novel genes, not previously described in the literature, which are subject to methylation-dependent transcriptional silencing in high-grade lymphoma and whose expression can be reactivated by demethylating agents. The novel genes encode proteins involved in diverse functional classes and include pro-apoptotic members of the p53 pathway (Scotin), transcriptional regulators (Baz2B) and regulators of telomerase (Smrf2). The frequency of methylation in individual genes varied from approximately 10% to 75% in specific lymphoma subtypes, but was in general similar in high grade lymphomas in immunocompetent and HIV-infected hosts. CONCLUSIONS: Using pharmacological reversal of methylation, we have identified a number of genes, not previously implicated in human neoplasia, which are subject to transcriptional silencing in high-grade B lymphomas. The similar frequencies of methylation, observed in immunocompetent and HIV positive patients implies that the genes are fundamental in suppression of lymphomagenesis. Detection of methylated DNA of one or more of these genes may have utility as biomarkers of
AU  - Bower,M
AU  - Syed,N
AU  - Papoudou-Bai,A
AU  - Stebbing,J
AU  - Naresh,K
AU  - Hatzimichael,E
AU  - Powles,S
AU  - Crook,T
PY  - 2009///
TI  - Methylation reversal in high-grade B lymphoma cell lines and novel epigenetic changes conserved between immunocompetent and HIV-positive hosts.
T2  - J Clin Oncol
UR  - http://www.ncbi.nlm.nih.gov/pubmed/27962294
VL  - 27
ER  -
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