Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias
| Autor: | Göran Roos, Krystyna H. Chrzanowska, Erik Forestier, Mattias Landfors, Sofie Degerman, W. Nicol Keith, Patrik Rydén, John Revie, Jan Konrad Siwicki, Emma Andersson Evelönn, Magnus Borssén |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Leukemia T-Cell T-Lymphocytes Biology lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Epigenetics of physical exercise Gene expression Medical Bioscience Cluster Analysis Humans Gene Regulatory Networks Cells Cultured 030304 developmental biology Regulation of gene expression 0303 health sciences Cancer och onkologi CpG Island Methylator Phenotype Gene Expression Regulation Leukemic Gene Expression Profiling Reproducibility of Results DEG differently expressed gene Methylation DNA Methylation lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens T-ALL T-cell acute lymphoblastic leukemia Molecular biology DMG differently methylated gene Gene expression profiling Medicinsk biovetenskap Cell Transformation Neoplastic CpG site CIMP CpG island methylator phenotype 030220 oncology & carcinogenesis Cancer and Oncology DNA methylation CpG Islands DM-CpG differently methylated CpG |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 16, Iss 7, Pp 606-615 (2014) Neoplasia (New York, N.Y.) |
| ISSN: | 1476-5586 1522-8002 |
| DOI: | 10.1016/j.neo.2014.07.001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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