Linking germline and somatic variation in Ewing sarcoma

  title={Linking germline and somatic variation in Ewing sarcoma},
  author={Nicholas C. Gomez and Ian J. Davis},
  journal={Nature Genetics},
The identification of gene-regulatory polymorphisms that influence cancer susceptibility can identify key oncogenic pathways. A new study links a germline variant to Ewing sarcoma disease susceptibility and EWSR1-FLI1–mediated gene activation. 
Germline genetic variants were interactively associated with somatic alterations in gastric cancer
Evidence is provided for the relationship between germline variants and somatic alterations, which facilitate understanding the interactive mechanism of germline variations with somatic alteration in gastric cancer development.
Pediatric Malignant Bone Tumors: A Review and Update on Current Challenges, and Emerging Drug Targets.
This review and update of pediatric malignant bone tumors will provide a general overview of osteosarcoma and the Ewing sarcoma family of tumors, discuss bone tumor genomics, current challenges, and emerging drug targets.
DNA Methylation and Regulatory Elements during Chicken Germline Stem Cell Differentiation
Summary The production of germ cells in vitro would open important new avenues for stem biology and human medicine, but the mechanisms of germ cell differentiation are not well understood. The


Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite
These findings establish cooperation between a dominant oncogene and a susceptibility variant that regulates a major driver of Ewing sarcomagenesis.
Microsatellites as EWS/FLI response elements in Ewing's sarcoma
It is found that EWS/FLI uses GGAA microsatellites to regulate the expression of some of its target genes including NR0B1, a gene required for Ewing's sarcoma oncogenesis and an unprecedented route to specificity for ETS proteins and use of microsatelliteites in tumorigenesis.
Clinical and Biochemical Function of Polymorphic NR0B1 GGAA-Microsatellites in Ewing Sarcoma: A Report from the Children's Oncology Group
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.
Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma
Variants at candidate risk loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2, and the major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence.
EWS/FLI-responsive GGAA microsatellites exhibit polymorphic differences between European and African populations.
The data suggest that GGAA microsatellite polymorphisms in the NR0B1 gene might influence disease susceptibility and prognosis in Ewing sarcoma in unanticipated ways.
Tumor-specific retargeting of an oncogenic transcription factor chimera results in dysregulation of chromatin and transcription.
It is found that in tumor cells, EWS-FLI targets regions of the genome distinct from FLI1, despite identical DNA-binding domains, which leads to mistargeting, chromatin disruption, and ultimately, transcriptional dysregulation.
EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma.
Divergent chromatin-remodeling patterns repress tumor suppressors and mesenchymal lineage regulators while activating oncogenes and potential therapeutic targets, such as the kinase VRK1.