Differential genome-wide array-based methylation profiles in prognostic subsets of chronic lymphocytic leukemia
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.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:115 |
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| Enthalten in: |
Blood - 115(2010), 2 vom: 14. Jan., Seite 296-305 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kanduri, Meena [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.01.2010 Date Revised 06.02.2021 published: Print-Electronic ErratumIn: Blood. 2014 Jan 9;123(2):300 Citation Status MEDLINE |
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| doi: |
10.1182/blood-2009-07-232868 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM192686380 |
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| 100 | 1 | |a Kanduri, Meena |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Differential genome-wide array-based methylation profiles in prognostic subsets of chronic lymphocytic leukemia |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a ErratumIn: Blood. 2014 Jan 9;123(2):300 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Cahill, Nicola |e verfasserin |4 aut | |
| 700 | 1 | |a Göransson, Hanna |e verfasserin |4 aut | |
| 700 | 1 | |a Enström, Camilla |e verfasserin |4 aut | |
| 700 | 1 | |a Ryan, Fergus |e verfasserin |4 aut | |
| 700 | 1 | |a Isaksson, Anders |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenquist, Richard |e verfasserin |4 aut | |
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