EWS/FLI-responsive GGAA microsatellites exhibit polymorphic differences between European and African populations.

@article{Beck2012EWSFLIresponsiveGM,
  title={EWS/FLI-responsive GGAA microsatellites exhibit polymorphic differences between European and African populations.},
  author={Robert Beck and Michael J. Monument and W. Scott Watkins and Richard D. Smith and Kenneth M. Boucher and Joshua D. Schiffman and Lynn B. Jorde and R Lor Randall and S. Lessnick},
  journal={Cancer genetics},
  year={2012},
  volume={205 6},
  pages={
          304-12
        }
}
The genetics of Ewing sarcoma development remain obscure. The incidence of Ewing sarcoma is ten-fold less in Africans as compared to Europeans, irrespective of geographic location, suggesting population-specific genetic influences. Since GGAA-containing microsatellites within key target genes are necessary for Ewing sarcoma-specific EWS/FLI DNA binding and gene activation, and gene expression is positively correlated with the number of repeat motifs in the promoter/enhancer region, we sought to… 
Clinical and Biochemical Function of Polymorphic NR0B1 GGAA-Microsatellites in Ewing Sarcoma: A Report from the Children's Oncology Group
TLDR
It is suggested that GGAA-microsatellite polymorphisms observed in human populations modulate EWS/FLI-mediated gene expression and may influence disease susceptibility in Ewing sarcoma.
Microsatellites with Macro-Influence in Ewing Sarcoma
TLDR
This unprecedented role of GGAA microsatellite DNA in Ewing sarcoma provides a unique opportunity to expand the mechanistic understanding of how EWS/FLI fusions influence cancer susceptibility, prognosis and transcriptional regulation.
Sequencing Overview of Ewing Sarcoma: A Journey across Genomic, Epigenomic and Transcriptomic Landscapes
TLDR
Using sequencing, novel predictive markers and candidates for immuno- and targeted therapy were identified and combined into a comprehensive overview of Ewing sarcoma.
Role for the EWS domain of EWS/FLI in binding GGAA-microsatellites required for Ewing sarcoma anchorage independent growth
TLDR
It is demonstrated in Ewing Sarcoma cells that EWS/FLI activates gene targets through binding at associated GGAA-microsatellites, and these repetitive sequences are necessary for Ewing sarcoma cell proliferation and anchorage-independent growth, and a previously unknown role for the EWS portion of the fusion protein as critical in binding at EWS /FLI targets is shown.
EWS/FLI1 Target Genes and Therapeutic Opportunities in Ewing Sarcoma
TLDR
This work describes a selection of EWS/FLI1 targets, their functional role, and their potential clinical relevance and discusses their role in other types of cancer as well as the need for further studies to be performed in order to achieve a broader understanding of their particular contribution to Ewing sarcoma development.
Genome-wide characterization of human minisatellite VNTRs: population-specific alleles and gene expression differences
TLDR
This study is the most comprehensive analysis of minisatellite VNTRs in the human population to date and validated the predictions in several ways, including experimentally, through the identification of predicted alleles in long reads, and by comparisons showing consistency between sequencing platforms.
Genome-wide characterization of human minisatellite VNTRs: population-specific alleles and gene expression differences
TLDR
This study is the most comprehensive analysis of minisatellite VNTRs in the human population to date and validated its predictions in several ways, including experimentally, through the identification of predicted alleles in long reads, and by comparisons showing consistency between sequencing platforms.
Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation
TLDR
The Ewing Sarcoma Cell Line Atlas (ESCLA) is presented, comprising 18 EwS cell lines with inducible EWSR1-ETS knockdown that were profiled by whole-genome-sequencing, DNA methylation arrays, gene expression and splicing arrays, mass spectrometry-based proteomics, and ChIP-seq for EWSR 1-ETS and histone marks.
TARGETED THERAPIES FOR EWSR1-FLI1 TRANSLOCATED EWING FAMILY OF TUMORS
TLDR
BCL-2 and BCL-XL act together to drive olaparib mediated apoptotic resistance in Ewing sarcoma and identify a novel, rational combination therapy using olapsarib and the BCL2/BCL-XL inhibitor navitoclax is revealed.
Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model
TLDR
Data is presented from six independent laboratories seeking an alternative approach to express EWS-FLI1 in different murine tissues using the Runx2, Col1a2.3, Col 1a3.6, Prx1, CAG, Nse, NEFL, Dermo1, P0, Sox9 and Osterix promoters to target E WS- FLI1 or Cre expression.
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