EWS–ETS oncoproteins: The linchpins of Ewing tumors

Janknecht, Ralf

doi:10.1016/j.gene.2005.08.007

Cited by 153 publications

(126 citation statements)

References 205 publications

(218 reference statements)

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“…The prototype fusion gene product is EWS/FLI1, which occurs in approximately 85% of cases (Lazar et al, 2006). These EWS/ets transcription factors are postulated to alter gene expression and centrally mediate tumor phenotype (Janknecht, 2005;Arvand and Denny, 2001). Many genes whose expression is enhanced or diminished by EWS/FLI1 have been identified (see Janknecht, 2005 for a review), though none of these targets has proven so crucial to tumor biology as to independently predict clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

The EWS/FLI1 oncogenic transcription factor deregulates GLI1

et al. 2007

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Ewing family tumors (EFT), classically Ewing's sarcoma and peripheral primitive neuroectodermal tumor, share a common class of tumor-specific fusion genes thought to be key mediators of tumor biology. Here we demonstrate that the most common Ewing's fusion, EWS/FLI1, produces transcriptional upregulation of GLI1 and its direct transcriptional target PATCHED1 in a model transformation system. This deregulation of GLI1 is common to other EWS/ets chimera and depends on the functional transcriptional regulatory domains. Inhibition of GLI1 via RNAi or via overexpression of endogenous inhibitors results in a reduction of EWS/FLI1 transformation activity. Activation of GLI1 appears to occur in a Hedgehog-independent fashion as blockade of Hedgehog signaling has only a modest effect on EFT cells. We present evidence that EWS/FLI1 upregulation of cMYC may play a role in the upregulation of GLI1 in EWS/ FLI1-transformed NIH3T3 cells. Finally, we demonstrate that observations made in a model transformation system translate to an Ewing cellular background. EFT cell lines express GLI1 and PATCHED and this expression is EWS/FLI1 dependent. Inhibition of GLI1 expression via RNAi results in reduced anchorage-independent growth in an EFT cell line. GLI1 appears to be a transcriptionally deregulated target of EWS/FLI1 that mediates a portion of its tumorigenic phenotype.

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Section: Introductionmentioning

confidence: 99%

The EWS/FLI1 oncogenic transcription factor deregulates GLI1

et al. 2007

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“…Irrespective of the EWS binding partner or precise structure of the hybrid transcript, the encoded protein always retains the C-terminal DNAbinding domain of the ETS transcription factor, highlighting the key role of this domain in cellular transformation (Janknecht, 2005). Analysis of alternative hybrid transcripts may also lead to information that is prognostically relevant.…”

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confidence: 99%

Diversity of TMPRSS2-ERG fusion transcripts in the human prostate

et al. 2006

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TMPRSS2-ERG gene fusions have recently been reported to be present in a high proportion of human prostate cancers. In the current study, we show that great diversity exists in the precise structure of TMPRSS2-ERG hybrid transcripts found in human prostates. Fourteen distinct hybrid transcripts are characterized, each containing different combinations of sequences from the TMPRSS2 and ERG genes. The transcripts include two that are predicted to encode a normal full-length ERG protein, six that encode N-terminal truncated ERG proteins and one that encodes a TMPRSS2-ERG fusion protein. Interestingly, distinct patterns of hybrid transcripts were found in samples taken from separate regions of individual cancercontaining prostates, suggesting that TMPRSS2-ERG gene fusions may be arising independently in different regions of a single prostate.

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“…The t(11;22)(q24;q12) translocation, a chromosomal abnormality specific to the Ewing's sarcoma, is detected in ~90% of cases (29). This translocation results in the formation of the EWS-FLI1 fusion gene (30). Another 10% of cases have a variant translocation fusing EWS to closely related EWS genes such as ERG, ETV1, EIAF, and FEV.…”

Section: Discussionmentioning

confidence: 99%

Extraskeletal Ewing's sarcoma of the thoracic epidural space: Case report and review of the literature

Yasuda

2011

Oncol Rep

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Abstract. The occurrence of primary extraskeletal Ewing's sarcoma (EES) of the spinal epidural space has been rarely reported in the literature. The clinical, radiologic and pathologic features of a case of EES occurring in the thoracic epidural space are presented. A 37-year-old woman presented with a one-year history of back pain. Magnetic resonance imaging demonstrated an epidural mass at the T8-9 level. Laminectomy and partial resection of the tumor were performed. The differential diagnosis of a spinal epidural mass is broad. Histopathological and molecular cytogenetic examinations confirmed an EES arising from the thoracic epidural space. Despite receiving both chemotherapy and radiotherapy, the patient died of respiratory insufficiency due to medulla oblongata metastasis 22 months after the initial consultation. Awareness of this entity will allow this rare diagnosis to be considered and facilitate appropriate management. A review of the literature on spinal epidural EES is also presented.

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EWS–ETS oncoproteins: The linchpins of Ewing tumors

Cited by 153 publications

References 205 publications

The EWS/FLI1 oncogenic transcription factor deregulates GLI1

The EWS/FLI1 oncogenic transcription factor deregulates GLI1

Diversity of TMPRSS2-ERG fusion transcripts in the human prostate

Extraskeletal Ewing's sarcoma of the thoracic epidural space: Case report and review of the literature

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