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450K-array analysis...
450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments
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- Cahill, Nicola (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Bergh, Ann-Charlotte (author)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Kanduri, Meena, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
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- Göransson-Kultima, H (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Mansouri, Larry (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Isaksson, Anders (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Ryan, F. (author)
- Institute of Technology, Dublin, Ireland
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- Smedby, K. E. (author)
- Karolinska Institutet
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- Juliusson, Gunnar (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Institute of Technology, Dublin, Ireland
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- Sundström, Christer (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Alafuzoff
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- Rosén, Anders (author)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Rosenquist, Richard (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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(creator_code:org_t)
- 2012-08-27
- 2013
- English.
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 27:1, s. 150-158
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://urn.kb.se/re...
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Abstract
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- In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K arrays, we provide the most comprehensive DNA methylation study of CLL to date, analyzing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n = 36) and patient-matched peripheral blood and lymph node samples (n = 20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (for example, CLLU1, LPL, ZAP70 and NOTCH1), epigenetic regulator (for example, HDAC9, HDAC4 and DNMT3B), B-cell signaling (for example, IBTK) and numerous TGF-beta and NF-kappa B/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event. Leukemia (2013) 27, 150-158; doi:10.1038/leu.2012.245
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- chronic lymphocytic leukemia
- DNA methylation
- 450K array
- prognostic
- subgroups
- compartments
- Pathology
- chronic lymphocytic leukemia; DNA methylation; 450K array; prognostic subgroups; compartments
Publication and Content Type
- art (subject category)
- ref (subject category)
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Leukemia
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- By the author/editor
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Cahill, Nicola
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Bergh, Ann-Charl ...
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Kanduri, Meena, ...
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Göransson-Kultim ...
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Mansouri, Larry
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Isaksson, Anders
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Ryan, F.
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Smedby, K. E.
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Juliusson, Gunna ...
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Sundström, Chris ...
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Rosén, Anders
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Rosenquist, Rich ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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Leukemia
- By the university
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Lund University
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Linköping University
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Uppsala University
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University of Gothenburg
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Karolinska Institutet