Immortalization of T-cells is accompanied by gradual changes in CpG methylation resulting in a profile resembling a subset of T-cell leukemias

Degerman, S. et al. (2014) Immortalization of T-cells is accompanied by gradual changes in CpG methylation resulting in a profile resembling a subset of T-cell leukemias. Neoplasia, 16(7), pp. 606-615. (doi:10.1016/j.neo.2014.07.001)

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Abstract

We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Keith, Professor Nicol
Authors: Degerman, S., Landfors, M., Siwicki, J. K., Revie, J., Borssén, M., Evelönn, E., Forestier, E., Chrzanowska, K. H., Rydén, P., Keith, W. N., and Roos, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Neoplasia
Publisher:Elsevier Inc.
ISSN:1522-8002
ISSN (Online):1476-5586
Copyright Holders:Copyright © 2014 Neoplasia Press, Inc.
First Published:First published in Neoplasia 16(7):606-615
Publisher Policy:Reproduced under a Creative Commons License

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