Microsatellites with macro-influence in Ewing sarcoma

Michael J. Monument, Kirsten M. Johnson, Allie H. Grossmann, Joshua D. Schiffman, R Randall, Stephen L. Lessnick

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Numerous molecular abnormalities contribute to the genetic derangements involved in tumorigenesis. Chromosomal translocations are a frequent source of these derangements, producing unique fusion proteins with novel oncogenic properties. EWS/ETS fusions in Ewing sarcoma are a prime example of this, resulting in potent chimeric oncoproteins with novel biological properties and a unique transcriptional signature essential for oncogenesis. Recent evidence demonstrates that EWS/FLI, the most common EWS/ETS fusion in Ewing sarcoma, upregulates gene expression using a GGAA microsatellite response element dispersed throughout the human genome. These GGAA microsatellites function as enhancer elements, are sites of epigenetic regulation and are necessary for EWS/FLI DNA binding and upregulation of principal oncogenic targets. An increasing number of GGAA motifs appear to substantially enhance EWS/FLI-mediated gene expression, which has compelling biological implications as these GGAA microsatellites are highly polymorphic within and between ethnically distinct populations. Historically regarded as junk DNA, this emerging evidence clearly demonstrates that microsatellite DNA plays an instrumental role in EWS/FLI-mediated transcriptional regulation and oncogenesis in Ewing sarcoma. This unprecedented role of GGAA microsatellite DNA in Ewing sarcoma provides a unique opportunity to expand our mechanistic understanding of how EWS/ETS fusions influence cancer susceptibility, prognosis and transcriptional regulation.

Original languageEnglish (US)
Pages (from-to)444-460
Number of pages17
JournalGenes
Volume3
Issue number3
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Fingerprint

Ewing's Sarcoma
Microsatellite Repeats
Carcinogenesis
DNA
Up-Regulation
Gene Expression
Genetic Translocation
Intergenic DNA
Oncogene Proteins
Response Elements
Human Genome
Epigenomics
Population
Neoplasms
Proteins

Keywords

  • ETS family transcription factors
  • EWS/FLI
  • Microsatellite DNA
  • Microsatellite polymorphisms
  • Oncogenesis
  • Transcriptional regulation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Monument, M. J., Johnson, K. M., Grossmann, A. H., Schiffman, J. D., Randall, R., & Lessnick, S. L. (2012). Microsatellites with macro-influence in Ewing sarcoma. Genes, 3(3), 444-460. https://doi.org/10.3390/genes3030444

Microsatellites with macro-influence in Ewing sarcoma. / Monument, Michael J.; Johnson, Kirsten M.; Grossmann, Allie H.; Schiffman, Joshua D.; Randall, R; Lessnick, Stephen L.

In: Genes, Vol. 3, No. 3, 01.09.2012, p. 444-460.

Research output: Contribution to journalReview article

Monument, MJ, Johnson, KM, Grossmann, AH, Schiffman, JD, Randall, R & Lessnick, SL 2012, 'Microsatellites with macro-influence in Ewing sarcoma', Genes, vol. 3, no. 3, pp. 444-460. https://doi.org/10.3390/genes3030444
Monument MJ, Johnson KM, Grossmann AH, Schiffman JD, Randall R, Lessnick SL. Microsatellites with macro-influence in Ewing sarcoma. Genes. 2012 Sep 1;3(3):444-460. https://doi.org/10.3390/genes3030444
Monument, Michael J. ; Johnson, Kirsten M. ; Grossmann, Allie H. ; Schiffman, Joshua D. ; Randall, R ; Lessnick, Stephen L. / Microsatellites with macro-influence in Ewing sarcoma. In: Genes. 2012 ; Vol. 3, No. 3. pp. 444-460.
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