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Differential genome...
Differential genome-wide array-based methylation profiles in prognostic subsets of chronic lymphocytic leukemia
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- Kanduri, Meena (författare)
- Uppsala universitet,Institutionen för genetik och patologi
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- Cahill, Nicola (författare)
- Uppsala universitet,Institutionen för genetik och patologi
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- Göransson, Hanna (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Cancer Pharmacology and Informatics
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- Enström, Camilla (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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Ryan, Fergus (författare)
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- Isaksson, Anders (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Cancer Pharmacology and Informatics
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- Rosenquist, Richard (författare)
- Uppsala universitet,Institutionen för genetik och patologi
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(creator_code:org_t)
- American Society of Hematology, 2010
- 2010
- Engelska.
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:2, s. 296-305
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Global hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27,578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in cell proliferation and tumor progression (eg, ADORA3 and PRF1 enhancing the nuclear factor-kappaB and mitogen-activated protein kinase pathways, respectively). In contrast, these latter genes were silenced by methylation in IGHV mutated patients. The array data were validated for selected genes using methylation-specific polymerase chain reaction, quantitative reverse transcriptase-polymerase chain reaction, and bisulfite sequencing. Finally, the significance of DNA methylation in regulating gene promoters was shown by reinducing 4 methylated tumor suppressor genes (eg, VHL and ABI3) in IGHV unmutated samples using the methyl-inhibitor 5-aza-2'-deoxycytidine. Taken together, our data for the first time reveal differences in global methylation profiles between prognostic subsets of CLL, which may unfold epigenetic silencing mechanisms involved in CLL pathogenesis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Haematology
- Hematologi
- Molecular medicine (genetics and pathology)
- Molekylär medicin (genetik och patologi)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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