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Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2014 (English)In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 16, no 7, 606-615 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2014. Vol. 16, no 7, 606-615 p.
National Category
Cancer and Oncology Medical Bioscience
Identifiers
URN: urn:nbn:se:umu:diva-93242DOI: 10.1016/j.neo.2014.07.001ISI: 000340553900006OAI: oai:DiVA.org:umu-93242DiVA: diva2:774188
Funder
Swedish Research Council, Dnr 340-2013-5185EU, FP7, Seventh Framework Programme, 200950
Available from: 2014-12-22 Created: 2014-09-15 Last updated: 2017-12-05Bibliographically approved

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Degerman, SofieLandfors, MattiasBorssen, MagnusEvelönn, EmmaForestier, ErikRyden, PatrikRoos, Göran

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