Pathogenic regulatory circuits in B cell lymphoma (HEM8P.238)
| Autor: | Olivia Koues, Rodney Kowalewski, Jennifer Schmidt, Sarah Pyfrom, Amanda Cashen, Jacqueline Payton, Eugene Oltz |
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| Rok vydání: | 2015 |
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| Zdroj: | The Journal of Immunology. 194:189.3-189.3 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.194.supp.189.3 |
| Popis: | Reprogramming gene expression via epigenetic perturbation of transcriptional control elements has emerged as a major mechanism of oncogenesis. Non-Hodgkin Lymphoma (NHL) is the most frequently diagnosed hematopoietic tumor. While distinct NHL gene expression patterns were identified a decade ago, underlying changes to the control elements driving these alterations remain poorly understood. Comparative integration of epigenome and transcriptome data from NHL cells and their normal counterpart B cells reveal the oncogenic regulatory circuitry that links differentially regulated control elements to target genes. Although many of these circuits are engaged in GC B cells or during B cell activation, a portion is commandeered from other cell lineages to promote transformation. Independent sets of transcription factors, whose expression are also deregulated in NHL, target augmented or attenuated circuit components. Importantly, these components are enriched for sequence variants that disrupt transcription factor binding and expression of circuit-linked genes. The pathogenic regulatory circuitry of NHL reveals genetic and epigenetic etiologies for B-cell transformation, providing unprecedented opportunity for therapeutic intervention. |
| Databáze: | OpenAIRE |
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