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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

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  • معلومة اضافية
    • Publisher Information:
      Umeå universitet, Patologi Umeå universitet, Institutionen för matematik och matematisk statistik Umeå universitet, Medicinsk och klinisk genetik 2014
    • نبذة مختصرة :
      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.
    • الموضوع:
      Cancer and Oncology; Cancer och onkologi; Medical Bioscience; Medicinsk biovetenskap; Article in journal; info:eu-repo/semantics/article; text
    • الرقم المعرف:
      10.1016.j.neo.2014.07.001
    • Availability:
      Open access content. Open access content
      info:eu-repo/semantics/openAccess
    • Note:
      application/pdf
      English
    • Other Numbers:
      UPE oai:DiVA.org:umu-93242
      0000-0002-2783-0712
      doi:10.1016/j.neo.2014.07.001
      ISI:000340553900006
      Scopus 2-s2.0-84928759013
      1234162490
    • Contributing Source:
      UPPSALA UNIV LIBR
      From OAIster®, provided by the OCLC Cooperative.
    • الرقم المعرف:
      edsoai.on1234162490
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