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Aberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease Severity
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نویسنده
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de s. ,shaknovich r. ,riester m. ,elemento o. ,geng h. ,kormaksson m. ,jiang y. ,woolcock b. ,johnson n. ,polo j.m. ,cerchietti l. ,gascoyne r.d. ,melnick a. ,michor f.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 1
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چکیده
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Despite mounting evidence that epigenetic abnormalities play a key role in cancer biology,their contributions to the malignant phenotype remain poorly understood. here we studied genome-wide dna methylation in normal b-cell populations and subtypes of b-cell non-hodgkin lymphoma: follicular lymphoma and diffuse large b-cell lymphomas. these lymphomas display striking and progressive intra-tumor heterogeneity and also inter-patient heterogeneity in their cytosine methylation patterns. epigenetic heterogeneity is initiated in normal germinal center b-cells,increases markedly with disease aggressiveness,and is associated with unfavorable clinical outcome. moreover,patterns of abnormal methylation vary depending upon chromosomal regions,gene density and the status of neighboring genes. dna methylation abnormalities arise via two distinct processes: i) lymphomagenic transcriptional regulators perturb promoter dna methylation in a target gene-specific manner,and ii) aberrant epigenetic states tend to spread to neighboring promoters in the absence of ctcf insulator binding sites. © 2013 de et al.
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آدرس
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department of medicine,university of colorado school of medicine,aurora,co,united states,molecular oncology program,university of colorado cancer center,aurora,co, United States, division of hematology/oncology,department of medicine,weill cornell medical college,new york,ny,united states,division of immunopathology,department of pathology,weill cornell medical college,new york,ny, United States, department of biostatistics and computational biology,dana-farber cancer institute,boston,ma,united states,department of biostatistics,harvard school of public health,boston,ma, United States, institute for computational biomedicine,weill cornell medical college,new york,ny, United States, division of hematology/oncology,department of medicine,weill cornell medical college,new york,ny,united states,institute for computational biomedicine,weill cornell medical college,new york,ny, United States, division of biostatistics and epidemiology,department of public health,weill cornell medical college,new york,ny, United States, division of hematology/oncology,department of medicine,weill cornell medical college,new york,ny, United States, centre for lymphoid cancers and departments of pathology and experimental therapeutics,british columbia cancer agency,british columbia cancer research centre,vancouver,bc, Canada, centre for lymphoid cancers and departments of pathology and experimental therapeutics,british columbia cancer agency,british columbia cancer research centre,vancouver,bc, Canada, monash immunology and stem cell laboratories,monash university,clayton, Australia, division of immunopathology,department of pathology,weill cornell medical college,new york,ny, United States, centre for lymphoid cancers and departments of pathology and experimental therapeutics,british columbia cancer agency,british columbia cancer research centre,vancouver,bc, Canada, division of hematology/oncology,department of medicine,weill cornell medical college,new york,ny, United States, department of biostatistics and computational biology,dana-farber cancer institute,boston,ma,united states,department of biostatistics,harvard school of public health,boston,ma, United States
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Authors
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