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)

The presence of t(11;22)(q24;q12) is often considered diagnostic of Ewing sarcoma and peripheral primitive neuroectodermal tumor. We report four cases, all of which possessed this translocation as detected by reverse transcriptase polymerase chain reaction and confirmed by sequencing with or without fluorescent in situ hybridization, but none of which were Ewing sarcoma or peripheral primitive neuroectodermal tumor by histological criteria. Two were polyphenotypic tumors and two were mixed embryonal and alveolar rhabdomyosarcomas. Only one case was positive for MIC2 by immunohistochemistry and only in a rare cell. Two cases (one polyphenotypic tumor and one rhabdomyosarcoma) had double minute chromosomes with > 100 copies of the MDM2 gene. The presence of the t(11;22)(q24;ql2) translocation should probably not be considered diagnostic of Ewing sarcoma and peripheral primitive neuroectodermal tumor in the absence of supporting histological evidence. The presence of this translocation in Ewing sarcoma and peripheral primitive neuroectodermal tumor has been taken as evidence that these two tumors are related. Extending this relationship to include some polyphenotypic tumors and some rhabdomyosarcomas may not be justified unless additional evidence is gathered. Pathologists and oncologists will need to decide whether treatment regimens for tumors are better based on phenotype rather than genotype when these two profiles are seemingly in conflict.
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PMID:Is the EWS/FLI-1 fusion transcript specific for Ewing sarcoma and peripheral primitive neuroectodermal tumor? A report of four cases showing this transcript in a wider range of tumor types. 864 55

This report describes an intra-abdominal desmoplastic small round-cell tumor in a 29-year-old man that significantly differed from the classically described appearances of this unique tumor. It showed extensive papillary areas, no necrosis, and very little desmoplasia. The latter was limited, paucicellular, and present in areas separate from the papillary structures. Also, areas of back-to-back, single-cell infiltration, which mimicked lobular breast carcinoma, were present. These epithelial features suggested the diagnosis of adenocarcinoma or peculiar mesothelioma. But, the immunohistochemical features (tumor cells positive for keratin, desmin, and vimentin) were more consistent with an intra-abdominal desmoplastic small round-cell tumor. The diagnosis became clear after application of reverse transcriptase-polymerase chain reaction techniques to formalin-fixed, paraffin-embedded tissue, which showed the presence of a 100-base pair product containing the fusion junction of Ewing's sarcoma-1 exon 7 to Wilms' tumor-1 exon 8. This feature is considered unique to intra-abdominal desmoplastic small round-cell tumors. This case illustrates the less common histologic findings that can be found in intra-abdominal desmoplastic small round-cell tumor. This deviation from the classic histologic findings may be an expression of an uncommon morphologic variant and/or partially produced by the effects of prior chemotherapy. In either event, only by illustrating the various histologic appearances of intra-abdominal desmoplastic small round-cell tumor are the chances increased for the accurate diagnosis of this aggressive neoplasm with a poor prognosis.
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PMID:Intra-abdominal desmoplastic small round-cell tumor: expansion of the pathologic profile. 878 11

Serial peripheral blood specimen from eight adult patients after sex-mismatched bone marrow transplantation (BMT) for Chronic Myeloid Leukemia (CML) (N = 3). Ewing sarcoma (N = 1), Acute Myeloid Leukemia (AML) in second remission (N = 1), Acute Lymphoid Leukemia (ALL) (N = 1), of multiple myeloma (N = 2) were analyzed by the simultaneous immunophenotypic (moAbs/ APAAP-staining) and genotypic analysis (for X and Y chromosomes) of interphase cells to characterize mixed chimerism, residual host cells, and leukemic relapse. Although a stable donor chimerism for T cells, myelomonocytic cells, and granulocytes was developed in seven of the eight patients at Days +21 to +28 post BMT, 0.5 to 1% host cells of different lineages remained continuously in five of the eight patients post BMT (> day 100). In two patients, one with common ALL and the other with multiple myeloma and long-term stable mixed chimerism, a tumor cell relapse was detected first in a sample at Day +176 and confirmed at Day +294. These malignant cells were genotypically of host origin and presented phenotypes identical to those at diagnosis. In the three patients with CML, residual host cells were identified as CD13 (Patient 3) of CD13/CD34 (Patient 4) positive and in one case as CD4/CD8 positive (Patient 7). Since no exclusive antigenic marker is available for this discrimination in these CML patients, normal host hematopoiesis can interfere with the identification of residual disease. Therefore, the identification of the bcr-abl transcripts by a two-step reverse transcriptase-polymerase chain reaction (RT-PCR) was included in this analysis. Patient 3 was bcr-abl positive at [Days +21, +28, +35, and +311, but negative at Days +121 and +400; Patient 4 was bcr-abl positive at only Day +166 post BMT. These results are interpreted as signaling a continuing risk of relapse. In Patient 7, the bcr-abl RT-PCR was negative at Days +142, +166, and +237. Thus, the combination of the simultaneous immunophenotypic and genotypic analysis and the bcr-abl detection by RT-PCR clearly improves the discrimination between malignant cells and normal residual host cells.
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PMID:Qualitative assessment of mixed chimerism after allogeneic bone marrow transplantation with regard to leukemic relapse. 893 46

The presence of t(11;22)(q24;q12) is often considered diagnostic of Ewing sarcoma and peripheral primitive neuroectodermal tumor (pPNET). We report a case of a polyphenotypic tumor that possessed this translocation as detected by reverse transcriptase polymerase chain reaction (RT-PCR). This tumor was positive for vimentin, desmin, low-molecular-weight keratin, neuron-specific enolase, S-100 protein, and CD57 by immunohistochemistry. Of note, the tumor was negative for MIC2. The tumor had double-minute chromosomes with > 100 copies of the MDM2 gene. Thus, the presence of the t(11;22)(q24;q12) translocation should not be considered diagnostic of Ewing sarcoma and pPNET in the absence of supporting histologic evidence such as positive staining for MIC2. The presence of this translocation in Ewing sarcoma and pPNET has been taken as evidence that these two tumors are related. Rather than extending this relationship to include some polyphenotypic tumors, other tumors may acquire this genetic change during tumor progression. Treatment regimens for tumors may be better based on phenotype rather than genotype when these two profiles are seemingly in conflict.
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PMID:Intra-abdominal polyphenotypic tumor. 896 28

The EWS/FLI1 fusion protein is created by the translocation between chromosomes 11 and 22 that appears in most Ewing's sarcomas. This chimeric protein has been demonstrated to be an aberrant transcription factor. Genes up regulated by EWS/FLI1 but not by full-length FLI1 were identified by representational difference analysis (RDA). We have characterized a novel gene, EWS/FLI1 activated transcript 2 (EAT-2) that was cloned from a murine cDNA library using a differentially expressed RDA fragment. EAT-2 expression is seen within 4-8 h of EWS/FLI1 induction. Its expression correlates with transformation of NIH3T3 cells by chimeric proteins related to EWS/FLI1 but not by unrelated genes. EAT-2 is expressed in normal murine tissues and contains a unique but biochemically functional SH2 domain. An homologous sequence in the human genome has been identified and mapped to chromosome 1q22. Human EAT-2 transcripts were identified by reverse transcriptase-polymerase chain reaction (RT-PCR) in Ewing's sarcoma cell tumour cell lines. EAT-2's unique structure and correlation with transformation make it a candidate for playing a role in the transformation of NIH3T3 cells and the oncogenesis of Ewing's sarcoma.
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PMID:EAT-2 is a novel SH2 domain containing protein that is up regulated by Ewing's sarcoma EWS/FLI1 fusion gene. 900 Jan 39

Ewing's sarcoma (ES) and other primitive peripheral neuroectodermal tumors (pPNETs) can present a significant diagnostic problem, as they may morphologically resemble other small round cell tumors (SRCTs) of childhood. However, ES/pPNET is known to carry a characteristic t(11;22)(q24;q12), the detection of which may aid diagnosis. The recent identification of the EWS and FLI-1 genes flanking the translocation break point has enabled reverse transcriptase-polymerase chain reaction (RT-PCR) to be used to detect the putative chimeric transcription factor mRNA produced by the fusion gene. We have assessed the RT-PCR method of detection by examining 40 cases of ES for the presence of EWS/FLI-1 transcripts. Twenty-six (76%) of the 34 cases with intact mRNA yielded fusion transcripts. Four different transcript sizes were detected and two tumors contained two transcripts of different size. No transcripts were detected in a control group of non-ES/pPNET SRCTs. Eight cases with intact mRNA were transcript negative. The MIC2 cell surface antigen, which is reported to be present in over 95% of ES/pPNETs, was present in 32 of 33 tumors (97%), including all 24 EWS/FLI-1 transcript-positive cases examined. Hence MIC2 is a useful screen for ES, with RT-PCR detection of t(11;22) being the optimal method for confirming the diagnosis.
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PMID:EWS/FLI-1 fusion transcript detection and MIC2 immunohistochemical staining in the diagnosis of Ewing's sarcoma. 902 40

Trk receptors have been identified by immunohistochemical methods in primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES). However, the presence of different members of the Trk family of receptors in PNET/ES has not been specified. We have examined whether Trk A, B, and C receptors are specifically expressed in ES both with and without features of neural differentiation. Ten ES tumors (five primary tumors of bone and five extraosseous tumors transplanted into nude mice) were investigated for expression of Trk receptors by immunohistochemistry and reverse transcription-polymerase chain reaction. One primary ES and the five grafted ES tumors exhibited signs of neural differentiation; the remaining four primaries were undifferentiated ES. Other tumor types were analyzed as controls; they included three neuroblastomas (NB), two lymphomas, and single cases of pheochromocytoma (PHEO), schwannoma (SCHW), osteosarcoma, and carcinoma of breast, colon, and kidney. Trk receptors were detected in paraffin-embedded tumor tissue sections by means of a pan-Trk polyclonal antibody raised against the 14 carboxy-terminal residues of gp140trk, and trk A, B, and C transcripts were specifically detected by polymerase chain reaction-based amplification on cDNAs derived from tumor RNA with MuLV reverse transcriptase. Reactivity to the pan-Trk antibody was exhibited by six ES tumors, the three NBs, and the single PHEO and SCHW cases; immunoreactivity was restricted to differentiated tumors, in the case of ES. Tumor types positive for immunostaining were also distinguished by containing transcripts of TRK genes. However, the trk A, B, and C expression pattern of ES differed from that of NBs, PHEO, and SCHW. Transcripts of trk A, B, and C were detected in seven, four, and one case of ES, respectively, and in five, two, and five cases of NB, PHEO, and SCHW, respectively. Interestingly, all differentiated ES tumors contained trk A transcripts. Tumors of neuroectodermal phenotype and/or derivation were thus characterized by a distinct consensus expression pattern: trk A+/B-/C+ for differentiated ES and trk A+/B-/C+ for NB-PHEO-SCHW. These results indicate that the TRK gene family is frequently activated in ES; they also suggest that Trk A receptor is a feature of ES with neural differentiation, whereas Trk B and C receptors seem to be present in undifferentiated ES.
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PMID:Activation of TRK genes in Ewing's sarcoma. Trk A receptor expression linked to neural differentiation. 902 32

EWS/ets-oncogene fusion transcripts can be detected in at least 98% of Ewing tumors [(ET) Ewing sarcoma and peripheral primitive neuroectodermal tumor] by reverse transcriptase-polymerase chain reaction (RT-PCR), thus confirming the histopathologic diagnosis. To detect minimal amounts of tumor cells in the bone marrow (BM), we used an RT-PCR assay with a high sensitivity, revealing one tumor cell in a background of 10(6) normal cells. We examined BM samples from 35 newly diagnosed ET patients (23 with localized and 12 with metastatic disease). At diagnosis, tumor cells in the BM were detected in 7/23 patients with localized disease (30%). Fifty percent of patients with isolated lung metastasis were RT-PCR positive (3/6), whereas 6/6 patients with bone metastases showed positive signals (100%). All patients with initial PCR positivity in the BM became negative during treatment. After a median follow-up of 30 months, relapses were observed in both groups of patients with localized disease (3/7 RT-PCR positive and 2/16 RT-PCR negative). The only recurrence in the group with isolated lung metastases occurred as progressive lung disease in 1 of the 2 RT-PCR-negative patients, whereas among the 6 patients with bone metastases 2 remain in complete remission. So far, RT-PCR screening for BM involvement did not allow prediction of early relapse in ET. To assess better the significance of this test in the evaluation of long-term prognosis and in monitoring the effectiveness of systemic therapy, long observation periods are warranted before it becomes a tool for treatment stratification.
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PMID:Predictive potential of testing for bone marrow involvement in Ewing tumor patients by RT-PCR: a preliminary evaluation. 949 59

Translocated in liposarcoma (TLS), a member of the Ewing's sarcoma family of RNA binding proteins, is targeted to the product of RNA POL II and functions in nuclear events as well as in nuclear-cytoplasmic transport of mRNA. It has been most extensively studied in cell lines, but was identified in several rat tissues by northern blot analysis, with adipose tissue showing the highest expression followed by whole skin. This paper describes a protein with amino acid sequence homology to TLS that was isolated from bovine tongue epithelium using an affinity column made with an antibody to the cornified envelope precursor sciellin. Using reverse transcriptase polymerase chain reaction technology and total RNA isolated from bovine tongue epithelium, a cDNA was obtained whose nucleotide sequence coded for a protein homologous to human TLS. Nuclear staining in all layers of human epidermis and bovine stratified epithelium was observed with an antibody to TLS, whereas peripheral staining of the upper layers of these tissues was observed with the antibody to sciellin. Cultured cells gave similar results; however, adult tissue required boiling in citrate buffer to unmask antigenic sites before reacting with the TLS antibody. Western blots of extracts of human and bovine keratinocytes using TLS and sciellin antibodies showed that the two proteins shared at least one epitope, but that they were different. TLS was lost from the nucleus following inhibition of RNA POL II activity and the protein was identified in CNBr extracts of purified keratinocytes cornified envelopes by western blot. These results clearly indicate that TLS functions as an RNA binding protein in keratinocytes in vivo and in vitro. Furthermore the sequestration of TLS to the cell envelope may play a role in regulating its nuclear-cytoplasmic transport and effect its role in transcription.
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PMID:Localization and characterization of the RNA binding protein TLS in skin and stratified mucosa. 950 49

During development, mice with mutations of stem cell factor (SCF) or its receptor c-kit exhibit defects in melanogenesis, as well as hematopoiesis and gonadogenesis. Consequently, accumulating evidence suggests that the c-kit/SCF system plays a crucial role in all of these processes and in tumors which derive from them. Especially in neuroblastoma (infant tumors of neuroectoderm crest derivation such as melanocytes) it would appear that an autocrine loop exists between c-kit and SCF, and that the functional block of the c-kit receptors with monoclonal antibodies (MoAbs) results in a significant decrease in cellular proliferation. We studied the expression and role of c-kit and SCF in cell lines of soft tissue sarcoma of neuroectodermic origin, such as Ewing's sarcoma (ES) and peripheral neuro-ectodermal tumors (PNET). Using flow cytometry with MoAb CD117 PE, c-kit expression was highlighted in all six of the cell lines examined. This receptor was specifically and functionally activated by SCF, as shown by the binding experiments and the intracellular phosphotyrosine and immunoprecipitation studies that were performed. Using reverse transcriptase polymerase chain reaction analysis, five of the six cellular lines expressed the mRNA of SCF. In the medium measured by using an enzyme- linked immunosorbent assay, low concentrations of SCF were found: only the TC32 cellular line produced significantly higher levels (32 pg) than control. In serum-free culture the addition of SCF reduced the percentage of apoptotic cells from 25% to 90% in five out of the six cellular lines. This observation was confirmed by (1) the functional block of c-kit with MoAb: after 7 days of culture more than 30% of the cells were apoptotic (range 31.5% to 100%) in five out of six cell lines and there was also a decrease in the percentage of cells in phase S, and (2) c-kit antisense oligonucleotides: in the cellular lines treated with oligonucleotides (in relation to the untreated lines) there was a notable reduction (P < .001) both in the absolute number of cells and the 3H-thymidine uptake. These results indicate that ES and PNET express c-kit and its ligand SCF and that SCF is capable of protecting the tumor cells against apoptosis. Furthermore, the reverse transcriptase-polymerase chain reaction performed on the biopsies revealed the presence of mRNA both of SCF and c-kit in practically all of the samples studied. Our in vitro data lead us to assume that SCF may also inhibit tumor cell apoptosis in vivo.
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PMID:c-kit is expressed in soft tissue sarcoma of neuroectodermic origin and its ligand prevents apoptosis of neoplastic cells. 951 39


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