Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias [Elektronisk resurs]
-
Degerman, Sofie (författare)
-
Landfors, Mattias (författare)
-
Siwicki, Jan Konrad (författare)
-
Revie, John (författare)
-
Borssen, Magnus (författare)
-
Evelönn, Emma (författare)
-
Forestier, Erik (författare)
-
Chrzanowska, Krystyna H. (författare)
-
Ryden, Patrik (författare)
-
Keith, W. Nicol (författare)
-
Roos, Göran (författare)
-
- Umeå universitet Medicinska fakulteten (utgivare)
-
-
Alternativt namn: Umeå universitet. Medicinsk-odontologiska fakulteten
-
Alternativt namn: Medicinska fakulteten vid Umeå universitet
-
Umeå universitet Teknisk-naturvetenskapliga fakulteten (utgivare)
-
- Umeå universitet Medicinska fakulteten (utgivare)
-
-
Alternativt namn: Umeå universitet. Medicinsk-odontologiska fakulteten
-
Alternativt namn: Medicinska fakulteten vid Umeå universitet
-
CLiC (medarbetare)
- 2014
- Engelska.
-
Ingår i: Neoplasia. - 1522-8002. ; 16:7, 606-615
-
Läs hela texten
-
Läs hela texten
-
Läs hela texten
Sammanfattning
Ämnesord
Stäng
- 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.
Ämnesord
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Cancer and Oncology (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Cancer och onkologi (hsv)
- Agricultural Sciences (hsv)
- Veterinary Science (hsv)
- Medical Bioscience (hsv)
- Lantbruksvetenskaper (hsv)
- Veterinärmedicin (hsv)
- Medicinsk biovetenskap (hsv)
Inställningar
Hjälp
Beståndsinformation saknas