The Ewing Family of Tumors -- A Subgroup of Small-Round-Cell Tumors Defined by Specific Chimeric Transcripts

Delattre, Olivier; Zucman, Jessica; Melot, Thomas; Garau, X S; Zucker, J M; Lenoir, Gilbert; Ambros, Peter F.; Sheer, Denise; Turc‐Carel, Claude; Triche, Timothy J.

doi:10.1056/nejm199408043310503

Cited by 975 publications

(528 citation statements)

References 16 publications

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“…Consistent cytogenetic alterations have been identified in several members of this family, including alveolar rhabdomyosarcoma, Ewing's sarcoma/peripheral neuroectodermal tumor (PNET), and desmoplastic small round cell tumor. 1 Recently, these chromosomal translocations have been characterized at the molecular level and found to result in PAX3-FKHR or PAX7-FKHR chimeric genes in alveolar rhabdomyosarcoma, 2 EWS-FLI1 and EWS-ERG gene fusions in Ewing's sarcoma/ PNET, 3 and EWS-WT1 gene fusions in desmoplastic small round cell tumor (DSRCT) 4 Chimeric transcripts and gene fusions specific for each translocation can be detected in clinical samples by reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH), and are proving to be a reliable and very useful diagnostic technique in the small round cell tumor family. 1,5 In this case study, we apply these molecular assays to detect chimeric transcripts in cytological specimens and peripheral blood samples in a sarcoma with neuroectodermal and muscle differentiation.…”

Section: Introductionmentioning

confidence: 99%

Molecular features in a biphenotypic small cell sarcoma with neuroectodermal and muscle differentiation

et al. 1998

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We report a case of a 13-year-old girl with soft tissue sarcoma of the hand, which showed muscle and neuroectodermal immunophenotypes. Molecular studies were performed on RNA collected from fine-needle aspiration (FNA) cytology and peripheral blood samples by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. This biphenotypic tumor showed simultaneous expression of EWS-FLI1 and PAX3-FKHR transcripts, specific of Ewing family tumors and alveolar rhabdomyosarcoma, respectively. Although childhood sarcomas with simultaneous muscle and neural differentiation have been described to have EWS-FLI1 transcripts, there are no reports of tumors with both transcripts. Cytological specimens are a good source of RNA for molecular studies. KEY WORDSMalignant ectomesenchymoma, Ewing sarcoma/PNET, alveolar rhabdomyosarcoma, EWS-FLI1 chimeric transcript, PAX3-FKHR chimeric transcript. ABBREVIATIONSRT-PCR, reverse transcription-polymerase chain reaction; FNA, fine-needle aspiration cytology; PNET, peripheral neuroectodermal tumor; MRI, magnetic resonance imaging; PBS, peripheral blood sample.

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Section: Introductionmentioning

confidence: 99%

Molecular features in a biphenotypic small cell sarcoma with neuroectodermal and muscle differentiation

et al. 1998

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“…ES/PNET is a family of tumors defined by a specific translocation involving the EWSR1 gene on chromosome 22q12 which is fused to an ETS gene family, most often to the FLI-1 gene on chromosome 11q24 or to the ERG gene on chromosome 21q22 and rarely to another ETS gene family. 10 This specific genetic abnormality can be routinely demonstrated by reverse transcriptase (RT)-PCR or by FISH. 10,11 The prognosis of bone and deep-seated soft tissue ES/PNET is poor despite various combinations of surgery, chemotherapy, and/or radiotherapy.…”

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“…10 This specific genetic abnormality can be routinely demonstrated by reverse transcriptase (RT)-PCR or by FISH. 10,11 The prognosis of bone and deep-seated soft tissue ES/PNET is poor despite various combinations of surgery, chemotherapy, and/or radiotherapy. In two small series, 7,8 it was suggested that superficial ES/PNET might have a more favorable prognosis.…”

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Superficial primitive Ewing's sarcoma: a clinicopathologic and molecular cytogenetic analysis of 14 cases

et al. 2009

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Superficial primitive Ewing's sarcomas are rare and have been reported to be of favorable prognosis compared to conventional deep-seated tumors. In the skin and subcutis, the diagnosis is often difficult, and performing molecular cytogenetic techniques may be helpful. We performed a retrospective analysis of 14 cases of superficial Ewing's sarcomas, all confirmed by molecular cytogenetics. Clinical, histological, immunohistochemical, molecular cytogenetic, therapeutic, and follow-up data are reported. There were 11 female and 3 male patients aged from 12 to 77 years (median: 17 years). Seven tumors occurred in the extremities, five in the trunk wall, and two in the head. Tumor size ranged from 1 to 5 cm (median, 3 cm). They were all small round-cell proliferations with a strong membranous positivity for CD99. Ewing's sarcoma translocations/fusion gene transcripts were detected in eight cases, both by FISH and reverse transcriptase (RT)-PCR. Four tumors were positive by RT-PCR alone (FISH not done in three cases and not interpretable in one case), and two cases were positive by FISH alone (RT-PCR not done). Surgical resection was performed in all patients. Chemotherapy was given in ten patients and radiotherapy in six. At last medical examination (median follow-up, 47 months), two patients who underwent surgical resection alone had died from the tumor. Our results confirm that superficial Ewing's sarcomas are of good prognosis. Given the difficulty of the diagnosis and the importance of an adapted treatment, a confirmation of the diagnosis by molecular or cytogenetic techniques is recommended when dealing with a superficial tumor.

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“…7 It can occur at any age but the vast majority (approximately 80%) occur before age 20 years. ES arises from neural crest cells [20][21][22] and can occur in any region of any bone often exhibiting an extensive soft-tissue component. 23 The hallmark genetic feature of ES is the t(11;22)(q24;q12) seen in 90-95% of cases or t(21;22)(q22;q12) translocation seen in 5-10% of cases.…”

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Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

et al. 2004

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Sarcomas, or tumors of connective tissue, represent roughly 20% of childhood cancers. Although the cure rate for sarcomas in general has significantly improved in the last 10 years, there continue to be subgroups that are difficult to treat. High-grade or metastatic soft-tissue sarcomas and rhabdomyosarcomas (RMS) of the extremities remain therapeutic challenges and their prognosis is often poor. The future of sarcoma therapy will likely include molecular approaches including gene/protein expression profiling and gene-based therapy. Most sarcomas harbor defects in the p53 or pRb pathways. The tumor suppressor p53 is central to regulation of cell growth and tumor suppression and restoring wild-type p53 function in pediatric sarcomas may be of therapeutic benefit. Studies with adenoviral-mediated p53 gene transfer have been conducted in many cancer types including cervical, ovarian, prostatic and head and neck tumors. Studies of this approach, however, remain limited in pediatric cancers, including sarcomas. Using three viral constructs containing cDNA for wild-type p53, mutant p53 (C135S) and lacZ, we studied the effect of adenoviralmediated gene therapy in four pediatric sarcoma cell lines, RD and Rh4 (RMS), Rh1 (Ewing's sarcoma) and A204 (undifferentiated sarcoma). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, we have shown a dose-dependent decrease in cell viability 72 h post-treatment that occurs with Ad-wtp53 but not with Ad-mutp53. Cells treated with Ad-wtp53 show upregulation of the p53 downstream targets, p21 CIP1/WAF1 and bax. Growth curves demonstrate suppression of cell growth over a period of 4 days and cells treated with Ad-wtp53 demonstrate a significant increase in sensitivity to the chemotherapeutic agents, cisplatin and doxorubicin. Our results indicate that restoration of wild-type p53 function in pediatric sarcoma cells could provide a basis for novel approaches to treatment of this disease.

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The Ewing Family of Tumors -- A Subgroup of Small-Round-Cell Tumors Defined by Specific Chimeric Transcripts

Cited by 975 publications

References 16 publications

Molecular features in a biphenotypic small cell sarcoma with neuroectodermal and muscle differentiation

Molecular features in a biphenotypic small cell sarcoma with neuroectodermal and muscle differentiation

Superficial primitive Ewing's sarcoma: a clinicopathologic and molecular cytogenetic analysis of 14 cases

Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

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