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EWS/FLI-1 rearrangement in small round cell sarcomas of bone and soft tissue detected by reverse transcriptase
1Department of Pathology, Medical School, University of Valencia, Spain.
Abstract:
Recent cloning of the t(11;22) region has led to the detection of a number of sequences involved in the breakpoints by substituting a sequence which encodes a putative RNA binding domain for that of the DNA binding domain of the human homologue of murine FLI-1. Several tumours display consistent translocation at t(11;22) (q24;q12), a finding that suggests these fusion transcripts could be expressed and detected by reverse transcriptase polymerase chain reaction amplification. To date, only a small number of Ewing's sarcomas (Es) and peripheral neuroectodermal tumours (pPNET) of bone have been tested with this novel molecular biology approach. In this study, we confirmed the presence of the three putative chimaeric transcripts on 7 cases of Es and pPNET sarcomas of bone and soft tissue, providing 100% positivity for the tested tumours. For comparative purposes, a number of other neuroectodermal tumours were analysed with negative results: esthesioneuroblastoma, retinoblastoma, Schwannoma. A primitive soft tissue sarcoma (ectomesenchymoma) with a 22 chromosome rearrangement did not express any transcript, nor did a number of non-neuroectodermal small round cell sarcomas of soft tissue (rhabdomyosarcomas) and bone (microcellular osteosarcoma), conventional bone sarcomas, leiomyosarcomas, malignant fibrous histiocytomas and synovial sarcomas. These results reinforce the value of molecular biology techniques for the correct assessment of histology difficult evaluable neoplasms, such as the group of small round cell tumours within the Es family.
Insights
This study confirms three fusion transcripts in Ewing
Area of Science:
- Molecular Oncology
- Cancer Genetics
- Diagnostic Pathology
Background:
- The t(11;22) translocation is a hallmark of Ewing's sarcoma (Es) and peripheral neuroectodermal tumors (pPNET).
- Fusion transcripts resulting from this translocation involve the FLI-1 gene and are potential diagnostic markers.
- Previous molecular detection of these transcripts in Es and pPNET has been limited.
Purpose of the Study:
- To investigate the prevalence of specific fusion transcripts in a cohort of Ewing's sarcoma family tumors.
- To evaluate the diagnostic utility of detecting these chimaeric transcripts using molecular methods.
- To differentiate Es/pPNET from other small round cell tumors.
Main Methods:
- Reverse transcriptase polymerase chain reaction (RT-PCR) amplification was used to detect fusion transcripts.
- Analysis focused on seven cases of bone and soft tissue Es and pPNET.
- Comparative analysis included other neuroectodermal and non-neuroectodermal tumors.
Main Results:
- All seven tested cases of Es and pPNET showed 100% positivity for the three putative chimaeric transcripts.
- Other neuroectodermal tumors (esthesioneuroblastoma, retinoblastoma, Schwannoma) were negative.
- Various other sarcomas, including rhabdomyosarcomas and osteosarcomas, did not express these transcripts.
Conclusions:
- The presence of these specific fusion transcripts is highly characteristic of Ewing's sarcoma and pPNET.
- Molecular detection via RT-PCR is a valuable tool for diagnosing difficult-to-evaluate small round cell tumors.
- This approach aids in distinguishing the Ewing's sarcoma family from other tumor types.