Project description:Although >90% of somatic mutations reside in non-coding regions, few have been reported as cancer drivers. To predict driver non-coding variants (NCVs), we present a novel transcription factor (TF)-aware burden test (TFA-BT) based on a model of coherent TF function in promoters. We applied our TFA-BT to NCVs from the Pan-Cancer Analysis of Whole Genomes cohort and predicted 2,555 driver NCVs in the promoters of 813 genes across 20 cancer-types. These genes are enriched in cancer-related gene ontologies, essential genes, and genes associated with cancer prognosis. We found that 765 candidate driver NCVs alter transcriptional activity, 510 lead to differential binding of TF-cofactor regulatory complexes, and that they primarily impact the binding of ETS factors. Finally, we show that different NCVs within a promoter often affect transcriptional activity through shared mechanisms. Our integrated computational and experimental approach shows that cancer NCVs are widespread and that ETS factors are commonly disrupted.

2023-01-10 | GSE218478 | GEO

Widespread perturbation of ETS factor binding sites in cancer [CASCADE_HOOK_SIGGERS_v3]

2023-01-09 | GSE222435 | GEO

Widespread perturbation of ETS factor binding sites in cancer [SCREEN_HOOK_SIGGERS_v2]

2023-01-09 | GSE222434 | GEO

Widespread perturbation of ETS factor binding sites in cancer

Project description:Although >90% of somatic mutations reside in non-coding regions, few have been reported as cancer drivers. To predict driver non-coding variants (NCVs), we present a transcription factor (TF)-aware burden test based on a model of coherent TF function in promoters. We apply this test to NCVs from the Pan-Cancer Analysis of Whole Genomes cohort and predict 2555 driver NCVs in the promoters of 813 genes across 20 cancer types. These genes are enriched in cancer-related gene ontologies, essential genes, and genes associated with cancer prognosis. We find that 765 candidate driver NCVs alter transcriptional activity, 510 lead to differential binding of TF-cofactor regulatory complexes, and that they primarily impact the binding of ETS factors. Finally, we show that different NCVs within a promoter often affect transcriptional activity through shared mechanisms. Our integrated computational and experimental approach shows that cancer NCVs are widespread and that ETS factors are commonly disrupted. Few cancer drivers in non-coding regions have been identified so far. Here, the authors develop a transcription factor-aware burden test to predict non-coding variants and analyze the impact on transcription factor binding - especially ETS factors - as well as their impact on transcriptional activity.

| S-EPMC9938127 | biostudies-literature

Widespread perturbation of ETS factor binding sites in cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-01-09 | GSE222436 | GEO

Shear stress switches the association of endothelial enhancers from ETV/ETS to KLF transcription factor binding sites

Project description:Shear stress switches the association of endothelial enhancers from ETV/ETS to KLF transcription factor binding sites

| PRJNA814612 | ENA

Genome-wide analysis of ETS factor ER71/ETV2 chromatin occupancy

Project description:We discover that ER71/ETV2 initiates hemangiogenic program by activating blood and endothelial cell lineage specifying genes while enhancing FLK1 expression and expanding hemangioblast population. Furthermore, ER71/ETV2 establishes an ETS hierarchy by directly activating Ets genes in hematopoietic and endothelial cell lineage development. As such, ER71/ETV2-initiated blood and endothelial cell program is maintained by ER71/ETV2 downstream ETS factors through an ETS switching mechanism. ChIP-seq analysis of ER71 in differentiated embryonic stem cells

2015-03-30 | E-GEOD-59402 | biostudies-arrayexpress

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