E2F4 plays a key role in Burkitt lymphoma tumorigenesis

Molina-Privado, Irene; Jiménez-P, R; Montes‐Moreno, Santiago; Chiodo, Yuri; Rodríguez-Martínez, María; Sánchez-Verde, Lydia; Iglesias, Teresa; Piris, Miguel Á.; Campanero, Miguel R.

doi:10.1038/leu.2012.99

Cited by 22 publications

(20 citation statements)

References 49 publications

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“…One of the anti-apoptotic genes located near a hypomethylated enhancer at relapse was BCL2 , a prognostic marker for the ABC-DLBCL subtype 37 . E2F4 has been reported to be downregulated in Burkitt lymphoma and upregulated in DLBCL 38 . Hypoxia-inducible factor controls the expression of genes in response to hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Epigenomic evolution in diffuse large B-cell lymphomas

et al. 2015

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The contribution of epigenomic alterations to tumour progression and relapse is not well characterized. Here we characterize an association between disease progression and DNA methylation in diffuse large B-cell lymphoma (DLBCL). By profiling genome-wide DNA methylation at single-base pair resolution in thirteen DLBCL diagnosis–relapse sample pairs, we show that DLBCL patients exhibit heterogeneous evolution of tumour methylomes during relapse. We identify differentially methylated regulatory elements and determine a relapse-associated methylation signature converging on key pathways such as transforming growth factor-β (TGF-β) receptor activity. We also observe decreased intra-tumour methylation heterogeneity from diagnosis to relapsed tumour samples. Relapse-free patients display lower intra-tumour methylation heterogeneity at diagnosis compared with relapsed patients in an independent validation cohort. Furthermore, intra-tumour methylation heterogeneity is predictive of time to relapse. Therefore, we propose that epigenomic heterogeneity may support or drive the relapse phenotype and can be used to predict DLBCL relapse.

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Section: Discussionmentioning

confidence: 99%

Epigenomic evolution in diffuse large B-cell lymphomas

et al. 2015

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“…E2F1 and E2F4 are also identified as TFs with higher activities in tumor epithelium samples, suggesting higher proliferative rate of malignant epithelium breast cells. E2F1 and E2F4 play the important regulatory role in cell cycle and many studies have demonstrated their importance during tumorigenesis [64,65]. In addition, ER alpha shows higher activity in malignant epithelium cells than in normal epithelium cells.…”

Section: Resultsmentioning

confidence: 99%

REACTIN: Regulatory activity inference of transcription factors underlying human diseases with application to breast cancer

2013

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BackgroundGenetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs.ResultsHere we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between ER+ and ER- samples in 10 breast cancer datasets. When applied to compare tumor and normal breast samples, it reveals TFs that are critical for carcinogenesis of breast cancer. Moreover, Reaction can be utilized to identify transcriptional programs that are predictive to patient survival time of breast cancer patients.ConclusionsREACTIN provides a useful tool to investigate regulatory programs underlying a biological process providing the related case and control gene expression data. Considering the enormous amount of cancer gene expression data and the increasingly accumulating ChIP-seq data, we expect wide application of REACTIN for revealing the regulatory mechanisms of various diseases.

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“…Related hub genes included E2F1, CDKN1A, PCNA, PIK3CG, PTEN and GTSE1. The role of E2F1 and E2F4 in the development of sporadic Burkitt's lymphoma (sBL) has been investigated (Molina-Privado et al, 2009, 2012. E2F1 is highly expressed by sBL cells and inhibition of its expression suppresses tumour formation.…”

Section: Discussionmentioning

confidence: 99%