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 Ewing family of tumours (ET) is characterised at the cytogenetic level by unique chromosome 22 rearrangements. The breakpoints have been cloned and were shown to fuse the EWS gene on chromosome 22 to one of two closely related ETS proto-oncogenes, FLI-I or ERG, which reside on chromosomes II and 21, respectively. The rearrangement results in the expression of chimaeric transcripts, which can be identified by means of reverse transcriptase-polymerase chain reaction (RT-PCR). We applied this method for the monitoring of ET cells circulating in the peripheral blood or infiltrating the bone marrow. The presence of tumour cells could be detected with a sensitivity of I in I x 10(6) nucleated cells. When samples were kept at 4 degrees C, tumour cells could still be identified after 48 hr of storage. Positive RT-PCR signals originated from intact ET cells rather than from free RNA released by ruptured tumour cells. We analysed peripheral blood, bone marrow samples and peripheral blood stem cell collections from 16 ET patients. At diagnosis, bone marrow specimens collected from 6 patients and I peripheral blood specimen tested positive for EWS chimaeric RNA. During therapy tumour cells were detected in bone marrow aspirations obtained from 2 patients. Our results show that ET cells infiltrating the bone marrow or circulating in peripheral blood can be identified by RT-PCR. The clinical implications for the presence of ET cells in samples detected by RT-PCR at diagnosis and during therapy requires further evaluation.
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PMID:Detection of tumour cells in peripheral blood and bone marrow from Ewing tumour patients by RT-PCR. 754 27

We have determined the frequency of EWS fusion transcripts in a series of primary Ewing's sarcomas and peripheral primitive neuroectodermal tumors and cells lines. Type 1 and 2 EWS-Fli1 fusions were demonstrated in 8 cell lines and 14 patient samples. Five patients with cytogenetically characterized rearrangements of chromosome 22 that did not involve chromosome 11 were included in these studies. A novel EWS-Fli1 in-frame isoform fusing EWS to exon 8 of Fli1 was isolated from a tumor with a variant t(12;22;22)(q14;p1;q12) translocation. Three in-frame isoforms of a novel hybrid transcript derived from the fusion of EWS with the ETS domain of the human erg gene were identified in patient samples and a cell line with cytogenetically unidentified or cryptic translocations involving chromosomes 21 and 22. Interphase analysis by fluorescent in situ suppression hybridization using two overlapping erg yeast artificial chromosome clones demonstrated disruption of the erg gene on chromosome 21 in a patient sample with monosomy 22. Our results provide new information about the involvement of EWS in small round cell tumors involving exchange of its putative RNA-binding domain with DNA-binding domains derived from different members of the ETS family of transcription factors. These studies emphasize the utility of reverse transcriptase PCR analysis and fluorescent in situ hybridization as additional diagnostic tools for differential diagnosis among small round cell tumors.
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PMID:EWS-erg and EWS-Fli1 fusion transcripts in Ewing's sarcoma and primitive neuroectodermal tumors with variant translocations. 804 Mar 1

We studied 116 patients (93 children and 23 adults) with acute lymphoblastic leukaemia (ALL) using fluorescence in situ hybridization (FISH) with the yeast artificial chromosome (YAC) clone, 964c10, which includes the recently described ETS-like gene, TEL, on 12p13. FISH revealed that nine of the patients had a t(12;21), which had not been previously detected. The nine patients were all children, seven boys and two girls, aged 1-10 years (median 3 years), had an early B immunophenotype, and achieved complete remission, although two of them experienced haematological relapse. In addition to the t(12;21), FISH also revealed that three of the nine had a del(12p) in the other homolog of chromosome 12 or in the der(12) chromosome itself, and that two others had 12p translocations in the other chromosome 12 homolog. Although chromosomal rearrangements associated with the t(12;21) were heterogenous and complex, fusion of the sequences from chromosomes 12 and 21 on the der(21)t(12;21) chromosomes was consistent, suggesting that the TEL-AML1 gene fusion on the der(21) chromosome may be critical in leukaemogenesis and that FISH or reverse transcriptase-polymerase chain reaction (RT-PCR) targeted to the chimaeric sequences on the der(21) will be most useful in detecting the t(12;21) or following a patient with the t(12;21), which is one of the most frequent chromosomal rearrangements in both Caucasian and Asian childhood ALL.
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PMID:The der(21)t(12;21) chromosome is always formed in a 12;21 translocation associated with childhood acute lymphoblastic leukaemia. 875 16

The members of the ETS family of transcription factors are grouped because they share a highly conserved DNA binding domain. These factors are involved in growth factor pathways and regulate both proliferation and differentiation. To identify ETS factors that may be involved in early hematopoietic progenitor regulation, we isolated a novel member of the ETS family by reverse transcriptase-PCR of the conserved DNA binding domain using degenerate oligonucleotides. This gene directs the synthesis of a 2704-nucleotide transcript whose largest open reading frame encodes a 548-amino-acid protein. Northern blot analysis reveals ubiquitous expression in all human tissues and cell lines tested, with highest levels in the testis, ovary, pancreas, and heart. Comparison of this gene with the available databases reveals very significant homology to the ETS factor PE-1 and probable near-identity with the recently cloned factor ERF. The PE-2 gene is composed of four exons spanning over 9 kb of genomic DNA. Sequence analysis of the promoter region reveals a GC-rich sequence without a TATA motif and with putative binding motifs for CREB, c-myb, and AP-1 factors. Using mouse-human somatic hybrids and FISH analysis, the PE-2 gene is localized to human chromosome 19q13.2, a region involved in translocations and deletions in leukemias and several solid tumors, suggesting that this novel ETS factor may play a role in carcinogenesis.
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PMID:Genomic structure and chromosomal localization of the novel ETS factor, PE-2 (ERF). 919 42

TEL is a new member of the ETS-like family on chromosome 12 and forms fusion genes with several partners in leukemia. Among these fusion genes, the TEL/AML1 translocation resulting from t(12;21) is found in approximately one quarter of the childhood B-cell lineage acute lymphoblastic leukemia (ALL) cases and its prognosis is excellent. We examined 42 adult patients with B-cell lineage ALL and 13 adult patients with lymphoblastic transformation of chronic myeloid leukemia (CML) to detect TEL/AML1 fusion genes using the reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting, but no translocation was detected. These findings indicate that absence of the TEL/AML1 fusion transcript partly correlates with the poorer outcome of adult B-cell lineage ALL as compared with childhood ALL and the TEL/AML1 fusion transcript is specific for pediatric B-cell lineage ALL.
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PMID:TEL/AML1 fusion gene resulting from a cryptic t(12;21) is uncommon in adult patients with B-cell lineage ALL and CML lymphoblastic transformation. 927 52

The t(12;21) (p13;q22) is observed in approximately 20-25% of childhood B-lineage acute lymphoblastic leukemia (ALL) cases in both Asian and Caucasian populations. This translocation results in the fusion of TEL, a recently described ETS-like gene on 12p13, and AML1, which was shown to be involved in the formation of fusion genes with ETO and EVI1 in myeloid leukemias. Fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis are useful in detecting this translocation which is not readily identified with routine cytogenetic techniques. The t(12;21) is associated with a distinct subgroup of patients characterized by an age between 1 and 10 years, an early B immunophenotype, and a good prognosis. A high incidence of the deletion of non-translocated TEL is another characteristic of leukemic cells with this translocation. TEL-AML1 hybrid protein thought to be critical in leukemogenesis possesses the HLH domain of TEL fused to almost the entire AML1 protein, although the detailed mechanisms of leukemogenesis remain obscure. RT-PCR combined with FISH analysis of posttreatment samples appears to be useful in detecting early relapse or minimal residual disease and thus, is expected to optimize the treatment strategy for patients with t(12;21).
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PMID:Detection of the Der (21)t(12;21) chromosome forming the TEL-AML1 fusion gene in childhood acute lymphoblastic leukemia. 949 2

Uropathogenic Escherichia coli (UPEC), the principal cause of urinary tract infection in women, attaches to the superficial facet cell layer of the bladder epithelium (urothelium) via its FimH adhesin. Attachment triggers exfoliation of bacteria-laden superficial facet cells, followed by rapid reconstitution of the urothelium through differentiation of underlying basal and intermediate cells. We have used DNA microarrays to define the molecular regulators of urothelial renewal and host defense expressed in adult C57Bl/6 female mice during the early phases of infection with isogenic virulent (FimH+) or avirulent (FimH-) UPEC strains. The temporal evolution and cellular origins of selected responses were then characterized by real time quantitative reverse transcriptase-PCR, in situ hybridization, and immunohistochemical analyses. Well before exfoliation is evident, FimH-mediated attachment suppresses transforming growth factor-beta (Bmp4) and Wnt5a/Ca(2+) signaling to promote subsequent differentiation of basal/intermediate cells. The early transcriptional responses to attachment also include induction of regulators of proliferation (e.g. epidermal growth factor family members), induction of the ETS transcription factor Elf3, which transactivates genes involved in epithelial differentiation and host defense (inducible nitric-oxide synthase), induction of modulators, and mediators of pro-inflammatory responses (e.g. Socs3, Cebp/delta, Bcl3, and CC/CXC chemokines), induction of modulators of apoptotic responses (A20), and induction of intermediate cell tight junction components (claudin-4). Both early and late phases of the host response exhibit remarkable specificity for the FimH+ strain and provide new insights about the molecular cascade mobilized to combat UPEC-associated urinary tract infection.
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PMID:Molecular regulation of urothelial renewal and host defenses during infection with uropathogenic Escherichia coli. 1174 8

A transcriptional repressor TEL belongs to the ETS family transcription factors and acts as a tumor suppressor. We identified five alternatively spliced TEL isoforms generated possibly through exon skipping mechanisms, by using reverse transcriptase-polymerase chain reaction analysis. Among them, we examined molecular and biological functions of a DeltaETS-TEL isoform (TEL-f). This isoform abrogated specific DNA-binding capacity to and trans-repressional ability through the ETS-binding site. Regardless, it showed dominant-negative effects over wild-type-TEL (TEL-a)-mediated transcriptional repression partly through sequestration of TEL-a from nucleus to cytoplasm. Moreover, TEL-f dominantly interfered with TEL-a-mediated erythroid differentiation in MEL cells and growth suppression in NIH3T3 cells. Interestingly, TEL isoforms without the entire (Delta exons 6+7-TEL) or a part (Delta exon 7-TEL) of ETS domain were expressed more frequently in myelodysplastic syndrome-derived leukemia than in myelodysplastic syndrome before transformation. This observation suggests that accumulation of the dominant-negative DeltaETS-TEL molecules could be a related phenomenon to leukemic progression of myelodysplastic syndrome.
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PMID:Functional analysis of a dominant-negative DeltaETS TEL/ETV6 isoform. 1509 86

The FMS-like tyrosine kinase 3 (FLT3) gene, belonging to the receptor tyrosine kinase (TK) subclass III family, plays an important role in normal hematopoiesis and is one of the most frequently mutated genes in hematologic malignancies as well as an attractive target for directed inhibition. Activating mutations of this gene, including internal tandem duplication in the juxtamembrane (JM) domain and point mutations in the TK domain, are found in approximately one-third of patients with acute myeloid leukemia and in a smaller subset of patients with acute lymphoblastic leukemia. We report here that FLT3 may contribute to leukemogenesis in a patient with myeloproliferative disorder and a t(12;13)(p13;q12) translocation through generating a fusion gene with the ETS variant gene 6 (ETV6) gene. ETV6 has been reported to fuse to various partner genes, including TK and transcription factors. Both ETV6/FLT3 and reciprocal FLT3/ETV6 transcripts were detected in the patient mRNA by reverse transcriptase-polymerase chain reaction. At the protein level, however, only ETV6/FLT3 products were expressed. Among them, one retains the helix-loop-helix (HLH) oligomerization domain of ETV6 and the JM as well as TK domain of FLT3. FLT3 receptor in leukemic cells might be inappropriately activated through dimerization by HLH domain of ETV6, which consequently interfered with proliferation and differentiation of hematopoietic cells.
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PMID:FLT3 is fused to ETV6 in a myeloproliferative disorder with hypereosinophilia and a t(12;13)(p13;q12) translocation. 1676 Oct 19

TMPRSS2:ERG gene fusions, the most common molecular subtype of ETS family gene fusions occur in ~50% of prostate carcinomas (PCas) and ~20% of high-grade prostatic intraepithelial neoplasia (HGPIN) intermingled with adjacent PCa demonstrating identical gene fusions. ERG gene fusions have not yet been demonstrated in isolated benign prostate tissue, isolated high-grade prostatic intraepithelial neoplasia, or benign cancer mimics. Taken together, ERG gene fusions are the most prostate cancer-specific biomarker yet identified and define a specific molecular subtype of PCa with important clinical and biological implications. ERG gene fusions result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG protein product. Recently, N-terminal epitope-targeted mouse (9FY) and C-terminal-targeted rabbit monoclonal (EPR 3864) ERG antibodies are commercially available and are increasingly utilized as a surrogate for TMPRSS2:ERG gene fusions. Until recently, because of lack of availability of reliable ERG antibody, the most commonly utilized methods for studying ERG aberrations in PCa specimens included fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction. The knowledge gleaned from these studies has significantly improved our understanding of molecular biology of ERG gene fusions. With availability of highly specific anti-ERG monoclonal antibodies, there are now unprecedented opportunities to explore and validate clinical applications of ERG antibody in routine pathology practice, which has just started. This review provides a brief background of molecular biology of ERG gene fusions in PCa and focuses on characterizing the current state of ERG oncoprotein and determining the role of ERG immunohistochemistry in the diagnosis and biological stratification of prostate cancer.
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PMID:Clinical applications of novel ERG immunohistochemistry in prostate cancer diagnosis and management. 2339 97


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