Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Childhood cutaneous and subcutaneous malignancies are rare and include metastatic tumors of diverse histogenesis as well as primary lesions, such as sweat gland carcinomas. Some cutaneous malignancies exhibit a small round cell tumor morphology with few definitive differentiating features; they can thus pose a significant diagnostic problem. We describe two primary malignancies of the skin and superficial subcutis, which were originally diagnosed as sweat gland carcinomas on the basis of their morphological features. A cytogenetic analysis performed on one of these lesions showed the t(11;22)(q24;q12) rearrangement, believed to be unique to the Ewing's sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) group of neoplasms. In view of this unexpected result, reverse transcriptase-polymerase chain reaction analysis was performed on both lesions and showed that they expressed EWS/FLI-1 fusion gene mRNA transcripts, the molecular equivalent of t(11;22)(q24;q12). The two tumors also had an immunohistochemical profile suggesting ES/pPNET, including strong expression of the MIC2 antigen. Both patients were treated with wide local excision, and one was given a course of chemotherapy. Neither patient showed evidence of tumor elsewhere after follow-up periods of 2 years and 16 years. These findings suggest that these tumors are indeed a form of primary ES/pPNET arising in the skin or superficial subcutis, which may be of low-grade malignancy and curable by local surgery.
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PMID:Primary cutaneous Ewing's sarcoma/peripheral primitive neuroectodermal tumors in childhood. A molecular, cytogenetic, and immunohistochemical study. 749 36

Desmoplastic small round cell tumor is a recently described entity associated with fusion of the EWS and WT1 genes and with expression of a chimeric transcript. To investigate the structure and potential diagnostic utility of the detection of EWS-WT1 chimeric RNA in desmoplastic small round cell tumor, 12 examples of this entity and 49 other tumors that enter in its differential diagnosis were studied by reverse transcriptase polymerase chain reaction for the presence of EWS-WT1, EWS-FLI-1, PAX3-FKHR, and PAX7-FKHR chimeric transcripts. EWS-WT1 was detected in 11 of 12 desmoplastic small round cell tumors but not in any other tumor type studied, including 17 Wilms' tumors, 10 Ewing's sarcomas/primitive neuroectodermal tumors, 13 alveolar rhabdomyosarcomas, and 9 embryonal rhabdomyosarcomas. One desmoplastic small round cell tumor was found to have a variant EWS-WT1 chimeric product that included exon 8 of EWS EWS-FLI-1 chimeric RNA was present in all Ewing's sarcoma/primitive neuroectodermal tumor and not identified in any other tumor types, including desmoplastic small round cell tumor. PAX3/PAX7-FKHR chimeras were present in 9 of 13 alveolar rhabdomyosarcomas but not in any other tumors. Detection of chimeric transcripts by reverse transcriptase polymerase chain reaction is a very specific aid in differential diagnosis of developmental tumors and further establishes desmoplastic small round cell tumor as a distinct entity.
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PMID:Detection of chimeric transcripts in desmoplastic small round cell tumor and related developmental tumors by reverse transcriptase polymerase chain reaction. A specific diagnostic assay. 749 83

The peripheral primitive neuroectodermal tumors (pPNETs) of childhood, including Ewing's sarcoma, peripheral neuroepithelioma, and Askin's tumor, often present significant diagnostic challenges for the anatomic pathologist. One consistent feature of these tumors is the presence of the t(11;22)(q24;q12) in tumor cells, and this translocation has been useful as a marker for this group of tumors. The recent cloning of the t(11;22) breakpoint has revealed the fusion of the human FLI-1 gene on chromosome 11q24 with a gene of unknown function called EWS on 22q12, and fusion transcripts have been detected. These findings have raised the possibility of using molecular genetic analysis as a tool to diagnose pPNETs. To this end, we have tested pPNETs for the presence of EWS/FLI-1 fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) using EWS and FLI-1 specific primers. Eight (80%) of 10 pPNET cell lines were positive for amplified products using this technique. These results were confirmed by Southern analysis, which revealed rearrangements of EWS using genomic EWS probes in all eight positive cell lines. We then tested 20 primary pPNET tumors, and identified fusion transcripts by RT-PCR in 18 (90%) of these cases. Cloning and sequencing of PCR products confirmed the presence of EWS and FLI-1 sequences in these products. Furthermore, fusion transcripts were not detected by this technique in a series of non-pPNET pediatric solid tumors. Detection of EWS/FLI-1 fusion transcripts by RT-PCR therefore provides a novel adjunctive tool in the diagnosis of pPNETs.
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PMID:Reverse transcriptase PCR amplification of EWS/FLI-1 fusion transcripts as a diagnostic test for peripheral primitive neuroectodermal tumors of childhood. 750 81

Recently, Ewing's tumours have been shown to carry specific hybrid transcripts resulting from the fusion of the EWS gene with FLI-1 or ERG genes. Based on the sensitivity and specificity of the detection of these alterations by the reverse transcriptase-polymerase chain reaction technique, we have developed an assay to search for small numbers of Ewing cells in various sites from patients with Ewing's tumour. This method enables the detection of fewer than one tumour cell per million blood mononuclear cells. A total of 28 primary sites and 51 peripheral samples from 36 patients were investigated. Tumour cells could be detected in 4/18 blood samples, 4/15 bone marrow aspirates and 2/18 peripheral stem cell harvests. EWS/FLI-1 and EWS/ERG transcripts being observed in eight and two cases respectively. The type of fusion transcript detected in peripheral site(s) was identical to that observed in the primary site. At diagnosis 5/16 patients (31%) demonstrated either circulating tumour cells or/and occult bone marrow metastasis. After induction therapy, tumour cells were detected in 3/21 patients. This highly sensitive method should be a relevant tool to allow a more accurate clinical assessment of the dissemination of Ewing's tumours.
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PMID:Sensitive detection of occult Ewing's cells by the reverse transcriptase-polymerase chain reaction. 759 72

Accurate diagnosis of primitive childhood sarcomas continues to be a formidable problem because these malignancies generally demonstrate very little morphological evidence of their tissue of origin. One of these tumor classes, the Ewing's sarcoma family of peripheral primitive neuroectodermal tumors (pPNETs), are thought to have a neural histogenesis based on evidence of neuroectodermal differentiation. Greater than 95% of pPNETs carry t(11;22) or t(21;22) chromosomal translocations which fuse the EWS gene from chromosome 22q12 in-frame with either FLI1 from chromosome 11q24 or ERG from chromosome 21q22. The pPNETs are considered to be histogenetically distinct from rhabdomyosarcomas, myogenic tumors lacking these EWS gene fusions and hypothesized to derive from immature skeletal muscle precursors. In the present study, we describe a unique set of childhood soft tissue sarcomas that show both neural and myogenic differentiation. These biphenotypic tumors express myogenic regulatory factors and muscle-specific antigens and also show neuroectodermal differentiation with ultrastructural evidence of neurosecretory granules and expression of neural-associated genes. Northern analysis and reverse transcriptase PCR reveal expression of EWS/FLI1 gene fusions in all biphenotypic sarcomas analyzed. Chimeric EWS/FLI1 transcripts and fusion proteins in these tumors are identical to those described for pPNETs. Our results provide evidence for a class of biphenotypic childhood sarcomas with myogenic and neural differentiation and suggest that these tumors may be related to the Ewing's sarcoma family of pPNETs.
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PMID:Biphenotypic sarcomas with myogenic and neural differentiation express the Ewing's sarcoma EWS/FLI1 fusion gene. 788 40

Cytogenetic analysis has defined specific translocations associated with two of the most common small round cell tumors of childhood, t(11;22) in Ewing's sarcoma and t(2;13) in alveolar rhabdomyosarcoma. We and others have previously demonstrated the diagnostic utility of a reverse transcriptase polymerase chain reaction (RT-PCR) assay for the detection of the t(11;22) encoded EWS/FLI-1 chimeric message in Ewing's sarcoma. More recently, we have cloned the t(2;13)(q35;q14) translocation and have shown that it results in the fusion of the PAX3 gene on chromosome 2 to FKHR, a novel member of the fork-head family of transcription factors on chromosome 13. To define the morphological spectrum of childhood sarcomas that express the t(2;13) encoded PAX3/FKHR chimeric message, we have performed RT-PCR analysis on samples from 44 primary pediatric sarcomas and 8 sarcoma cell lines. PAX3/FKHR chimeric messages were detected in 24 of 27 alveolar, 2 of 12 embryonal, and 0 of 1 pleomorphic rhabdomyosarcoma and in 1 of 2 ectomesenchymomas. In contrast, none of 8 Ewing's sarcomas or 2 undifferentiated sarcomas expressed this message. Chimeric transcripts were detected in all cases with cytogenetic evidence of the (2;13) translocation, and in each case the chimeric PAX3/FKHR message had the identical junction sequence, suggesting that genomic chromosome breaks were clustered in a single intron in both genes. By combining the PAX3/FKHR RT-PCR assay with primers for detection of the Ewing's sarcoma t(11;22) encoded EWS/FLI-1 chimeric transcript, we have developed a multiplex RT-PCR reaction that allows the rapid and accurate identification of either translocation in a biopsy sample.
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PMID:Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma. 788 45

The desmoplastic small round cell tumor (DSRCT) is a recently recognized type of primitive sarcoma defined by a predilection for young males, aggressive clinical behavior, widespread abdominal serosal involvement, and a primitive histological appearance with prominent desmoplasia and striking divergent, multilineage differentiation. Previous cytogenetic case reports have identified a recurrent translocation, t(11;22) (p13;q12). We have characterized this translocation at the molecular level in a panel of five DSRCTs using a candidate gene approach. Southern blot analysis revealed recurrent rearrangement of both EWS, located at 22q12, and rearranged in other tumor-specific translocations in Ewing's sarcoma and clear cell sarcoma, and of WT1, the gene at 11p13 involved in a subset of Wilms' tumor. Consistent comigration of the rearranged EWS and WT1 bands in multiple enzyme digests indicated fusion of the genomic sequences, presumably due to the translocation t(11;22) (p13;q12). Northern blotting showed aberrant EWS and WT1 transcripts of the same size, suggesting the presence of a chimeric messenger RNA. This was confirmed by reverse transcriptase polymerase chain reaction using an EWS exon 7 primer and WT1 exon 8 or 9 primers, which revealed single polymerase chain reaction products consistent with a junction of EWS exon 7 to WT1 exon 8. DSRCT thus represents the third primitive sarcoma in which the EWS gene is involved and the first instance of recurrent rearrangement of a tumor suppressor gene, WT1, in a specific tumor type. The different translocation partners of the EWS gene, all of which are putative or definite transcription factor genes, may be responsible for the biological differences between DSRCT, Ewing's sarcoma, and clear cell sarcoma.
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PMID:Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. 818 63

Chromosomal translocations have been identified that are consistently associated with alveolar rhabdomyosarcoma and Ewing's sarcoma. Molecular diagnostic assays for these chromosomal translocations are important tools for the differential diagnosis of pediatric small round cell tumors presenting in the bones or soft tissues. However, the occurrence of variant chromosomal translocations in these cancers has complicated these molecular diagnostic approaches. To simplify the molecular detection of typical and variant translocations, the authors have developed an approach consisting of consensus reverse transcriptase-polymerase chain reaction and oligonucleotide hybridization steps. In the first step, consensus primers for each tumor type permit amplification of the chimeric transcripts resulting from both the common and variant translocations. In the second step, the common and variant translocations are distinguished by hybridization with gene-specific oligonucleotide probes. This approach provides a sensitive, specific, and efficient strategy for the detection of these chromosomal translocations.
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PMID:A consensus polymerase chain reaction-oligonucleotide hybridization approach for the detection of chromosomal translocations in pediatric bone and soft tissue sarcomas. 852 4

We report two cases of intra-abdominal desmoplastic small round cell tumor with characteristic clinical, histological, immunohistochemical, and ultrastructural features. Fusion of the EWS gene on chromosome 22 and the WT1 gene on chromosome 11, resulting from the chromosomal translocation t(11;22)(p13;q12), was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in both cases. This translocation has been previously reported in this type of tumor using either cytogenetic or molecular biological techniques. Tumor tissue from both cases revealed no chimeric fusion transcripts characteristic of the Ewing sarcoma family of peripheral primitive neuroectodermal tumors or of alveolar rhabdomyosarcoma, two tumors in the differential diagnosis of intra-abdominal desmoplastic small round cell tumor. This report demonstrates the utility of molecular studies as an adjunct in the diagnosis of this rare and aggressive tumor.
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PMID:Detection of the EWS/WT1 gene fusion by reverse transcriptase-polymerase chain reaction in the diagnosis of intra-abdominal desmoplastic small round cell tumor. 860 6

The identification of Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET) among other small round cell tumors (SRCTs) is a critical issue in musculoskeletal pathology because of the lack of clearly distinctive morphological features. In this study, the authors have compared advantages and limits of two procedures that were recently suggested as additional tools for the identification of ES/PNET, the analysis of p30/32MIC2 antigen by immunohistochemistry, and the evaluation of the fusion products of two specific chromosomal aberrations, the t(11;22)(q24;q12) and the t(21;22)(q22;q12), by reverse transcriptase-polymerase chain reaction (RT-PCR). The authors have analyzed the expression of p30/32MIC2 in 28 cell lines and in 90 tumor samples. p30/32MIC2 was highly expressed in ES/PNET but was also present in all the other cell types. The broad spectrum of positivity for p30/32MIC2 in SRCTs of bone was substantially confirmed by the analysis of tissue samples. In the same material, the authors have evaluated the presence of t(11;22) or t(21;22) transcripts (EWS/FLI-1 and EWS/ERG, respectively) by RT-PCR. These transcripts were found in all the cell lines and tissue samples of ES/PNET, but not in other tumors. The authors' results question the use of p30/32MIC2 immunostaining alone for the identification of ES/PNET and suggest the adoption of RT-PCR as an advantageous alternative. Molecular diagnosis of ES/PNET by RT-PCR is highly specific and can be applied to small amounts of tissue. Moreover, RNA extracted from paraffin-embedded specimens was shown to be suitable for RT-PCR analysis, thus enabling analysis of archival material.
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PMID:Immunostaining of the p30/32MIC2 antigen and molecular detection of EWS rearrangements for the diagnosis of Ewing's sarcoma and peripheral neuroectodermal tumor. 861 85


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