A Gene Panel, Including LRP12, Is Frequently Hypermethylated in Major Types of B-Cell LymphomaReportar como inadecuado

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Epigenetic modifications and DNA methylation in particular, have been recognized as important mechanisms to alter gene expression in malignant cells. Here, we identified candidate genes which were upregulated after an epigenetic treatment of B-cell lymphoma cell lines Burkitt-s lymphoma, BL; Follicular lymphoma, FL; Diffuse large B-cell lymphoma, DLBCL activated B-cell like, ABC; and germinal center like, GCB and simultaneously expressed at low levels in samples from lymphoma patients. Qualitative methylation analysis of 24 candidate genes in cell lines revealed five methylated genes BMP7, BMPER, CDH1, DUSP4 and LRP12, which were further subjected to quantitative methylation analysis in clinical samples from 59 lymphoma patients BL, FL, DLBCL ABC and GCB; and primary mediastinal B-cell lymphoma, PMBL. The genes LRP12 and CDH1 showed the highest methylation frequencies 94% and 92%, respectively. BMPER 58%, DUSP4 32% and BMP7 22%, were also frequently methylated in patient samples. Importantly, all gene promoters were unmethylated in various control samples CD19+ peripheral blood B cells, peripheral blood mononuclear cells and tonsils as well as in follicular hyperplasia samples, underscoring a high specificity. The combination of LRP12 and CDH1 methylation could successfully discriminate between the vast majority of the lymphoma and control samples, emphasized by receiver operating characteristic analysis with a c-statistic of 0.999. These two genes represent promising epigenetic markers which may be suitable for monitoring of B-cell lymphoma.

Autor: Nicole Bethge, Hilde Honne, Kim Andresen, Vera Hilden, Gunhild Trøen, Knut Liestøl, Harald Holte, Jan Delabie, Guro E. Lind, Er

Fuente: http://plos.srce.hr/


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