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Extensive promoter DNA hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia

Title
Extensive promoter DNA hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia
Authors
Baer C.Claus R.Frenzel L.P.Zucknick M.Park Y.J.Gu L.Weichenhan D.Fischer M.Pallasch C.P.Herpel E.Rehli M.Byrd J.C.Wendtner C.-M.Plass C.
Ewha Authors
박윤정
SCOPUS Author ID
박윤정scopus
Issue Date
2012
Journal Title
Cancer Research
ISSN
0008-5472JCR Link
Citation
vol. 72, no. 15, pp. 3775 - 3785
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Dysregulated microRNA (miRNA) expression contributes to the pathogenesis of hematopoietic malignancies, including chronic lymphocytic leukemia (CLL). However, an understanding of the mechanisms that cause aberrant miRNA transcriptional control is lacking. In this study, we comprehensively investigated the role and extent of miRNA epigenetic regulation in CLL. Genome-wide pro filing conducted on 24 CLL and 10 healthy B cell samples revealed global DNA methylation patterns upstream of miRNA sequences that distinguished malignant from healthy cells and identified putative miRNA promoters. Integration of DNA methylation and miRNA promoter data led to the identification of 128 recurrent miRNA targets for aberrant promoter DNA methylation. DNA hypomethylation accounted for more than 60% of all aberrant promoter-associated DNA methylation in CLL, and promoter DNA hypomethylation was restricted to well-defined regions. Individual hyper- and hypomethylated promoters allowed discrimination of CLL samples from healthy controls. Promoter DNA methylation patterns were con firmed in an independent patient cohort, with 11 miRNAs consistently showing an inverse correlation between DNA methylation status and expression level. Together, our findings characterize the role of epigenetic changes in the regulation of miRNA transcription and create a repository of disease-specific promoter regions that may provide additional insights into the pathogenesis of CLL. ©2012 AACR.
DOI
10.1158/0008-5472.CAN-12-0803
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신산업융합대학 > 식품영양학과 > Journal papers
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