Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myxoid liposarcomas are cytogenetically characterized by t(12;16)(q13;p11). The translocation results in rearrangements of the CHOP gene in 12q13 and the FUS gene in 16p11, creating a fusion gene where the RNA-binding domain of FUS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. In the present study, we have mapped 16 genomic breakpoints in the region of the CHOP gene and isolated and sequenced a new variant (type II) of the chimeric FUS/CHOP transcript. The genomic breakpoints were dispersed along a 7.50-kilobase pair region from a SstI cleavage site upstream of the promoter of CHOP to a PstI cleavage site within intron 1. Reverse transcriptase-polymerase chain reaction analysis of tumor samples demonstrated the presence of two variant fragments, 654 base pairs (type I) and 378 base pairs (type II) in size. Of the 13 samples analyzed, 7 showed the smaller, 3 showed the larger, and 3 showed both types of transcripts. We cloned and sequenced the two fragments and found in type II a novel fusion point in the FUS mRNA 275 base pairs upstream of that present in the type I transcript. In both types of transcripts the interrupted FUS is followed by the entire exon 2 of CHOP. As a consequence the normally nontranslated exon 2 is translated and in both types there is in the junction between FUS and CHOP a shift from a FUS glycine codon to a valine codon in the chimeric mRNA.
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PMID:Characterization of the CHOP breakpoints and fusion transcripts in myxoid liposarcomas with the 12;16 translocation. 798 49

Low-grade fibromyxoid sarcoma (LGFMS) is an indolent, late-metastasizing malignant soft-tissue tumor that is often mistaken for either more benign or more malignant tumor types. Cytogenetic analyses have identified a recurrent balanced translocation t(7;16) (q32-34;p11), later shown by molecular genetic approaches to result in a FUS/CREB3L2 fusion gene. Whereas preliminary studies suggest that this gene rearrangement is specific for LGFMS, its incidence in this tumor type and the possible existence of variant fusion genes have not yet been addressed. For this purpose, a series of potential LGFMS were obtained from nine different soft-tissue tumor centres and subjected to molecular analysis as well as careful histopathologic review. Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive. In one of the tumors with typical LGFMS appearance, we found that FUS was fused to the CREB3L1 gene instead of CREB3L2. The proteins encoded by these genes both belong to the same basic leucine-zipper family of transcription factors, and display extensive sequence homology in their DNA-binding domains. Thus, it is expected that the novel FUS/CREB3L1 chimera will have a similar impact at the cellular level as the much more common FUS/CREB3L2 fusion protein. Taken together, the results indicate that virtually all LGFMS are characterized by a chimeric FUS/CREB3L2 gene, and that rare cases may display a variant FUS/CREB3L1 fusion.
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PMID:Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene. 1564 Aug 31

This study reports a 1-year-old boy with precursor B cell acute lymphoblastic leukemia (ALL) carrying t(16;21)(p11;q22). Reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequence analysis showed TLS/FUS-ERG chimeric mRNA with a novel junctional pattern of exon 7 of TLS/FUS and exon 6 of ERG. He did not respond to ALL-oriented therapy. Complete remission (CR) was achieved by chemotherapy oriented for acute myeloid leukemia. Allogenic bone marrow transplantation was done and he has been in CR for 24 months. TLS/FUS-ERG chimeric mRNA was not detected after CR. This is the first report of an ALL patient with a TLS/FUS-ERG fusion transcript.
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PMID:TLS/FUS-ERG fusion gene in acute lymphoblastic leukemia with t(16;21)(p11;q22) and monitoring of minimal residual disease. 1626 89

We report on a case of pediatric acute myelocytic leukemia showing 47,XX,+10,t(16;21)(p11;q22) that resulted in an unusual TLS/FUS-ERG chimeric transcript. The leukemic cells showed erythrophagocytosis, positive reactions for myeloperoxidase and Sudan black B stains, and negative reactions for periodic acid-Schiff and alpha-naphtyl butyrate esterase stains as well as expression of myeloid antigens. We also confirmed a very rare type of TLS/FUS-ERG chimeric transcript by fusion of the 5' part of the TLS/FUS gene in chromosome 16p11 and the 3' part of the ERG gene in chromosome 21q22 using reverse-transcriptase polymerase chain reaction and direct sequencing. After achieving a complete remission with two cycles of induction chemotherapy, the patient received an umbilical cord blood transplantation.
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PMID:Unusual type of TLS/FUS-ERG chimeric transcript in a pediatric acute myelocytic leukemia with 47,XX,+10,t(16;21)(p11;q22). 1673 20

We report two childhood cases of acute leukemia with t(16;21)(p11.2;q22) and FUS-ERG rearrangements. Patient 1 (14 years old) was initially diagnosed with acute myeloid leukemia. Chromosome study showed a t(16;21)(p11.2;q22) clone in more than one third of the cells analyzed, and further investigation with reverse-transcriptase polymerase chain reaction, cloning, and sequencing confirmed FUS-ERG rearrangement (type B). Patient 2 (8 months old) was diagnosed with acute lymphoblastic leukemia (ALL) on the basis of bone marrow morphology and immunophenotyping. Chromosome study revealed a 45,XY,-16,der(21)t(16;21)(p11.2;q22) in 50% of the cells analyzed. Further studies for the detection of a FUS-ERG chimeric transcript were conducted, and an unusual type of FUS-ERG rearrangement was discovered, which has been reported in only three patients including a 1-year-old infant with ALL. Although more clinical studies are necessary, we believe that a possible association between ALL and a specific type of FUS-ERG fusion transcript might be considered, especially in childhood cases with t(16;21).
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PMID:Two childhood cases of acute leukemia with t(16;21)(p11.2;q22): second case report of infantile acute lymphoblastic leukemia with unusual type of FUS-ERG chimeric transcript. 2062 Jun 4

FUS-ERG gene fusion has not been reported in cases of myeloid sarcoma (MS), a subtype of acute myeloid leukemia involving extramedullary anatomic sites. Here, we report a case of a 48-year-old man with primary isolated MS of the anterior mediastinum, who later developed multiple extramedullary recurrences without bone marrow infiltration throughout the course. G-banding analysis of the cells in pericardial effusion at recurrence showed complex karyotypic abnormalities including t(16;21)(p11.2;q22). FUS break-apart fluorescent in situ hybridization analysis showed split signals in biopsy sections at initial diagnosis and recurrence. Reverse transcriptase polymerase chain reaction and direct sequencing demonstrated the presence of the FUS-ERG chimeric gene transcript. The patient underwent cord blood transplantation, but died of pneumonia on day 64. To our knowledge, this is the first report of isolated MS carrying FUS-ERG gene fusion. In future study, relationship between the fusion gene and uncommon clinical features should be investigated in isolated MS.
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PMID:FUS-ERG gene fusion in isolated myeloid sarcoma showing uncommon clinical features. 2677 Aug 12

The t(16;21)(p11;q22) is a rare chromosomal abnormality that appears in approximately 1% of acute myeloid leukemia (AML) cases. Previously, between 50 and 60 cases have been reported. In this review, we will discuss the literature regarding t(16;21) as well as cases published. We compiled 68 cases from the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer as well as 10 additional cases in the literature, for a total of 78 cases. The t(16;21) results in the TLS(FUS)-ERG fusion protein, which is believed to function as a transcriptional activator in leukemogenesis and has been demonstrated to interfere in normal pre-mRNA splicing functions of FUS/TLS. Reverse-transcriptase polymerase chain reaction of fusion transcripts in patients, has been demonstrated to have diagnostic significance in monitoring for minimal residual disease. Cytogenetically, about half of the cases had secondary chromosomal abnormalities; we found that trisomy 8 and 10 were the most common abnormalities, occurring in 9.1% of the otal cases for each. t(16;21) in AML has been described with various morphological features, such as phagocytosis and vacuolation, and is present in multiple FAB types. Immunophenotypic characteristics such as CD33 and CD34 expression have also been noted, and several studies have examined the relation between CD56 receptor expression and t(16;21) AML. In general, t(16;21) in AML is associated with a poor prognosis and this abnormality could serve as cytogenetic indicator in determining diagnosis and prognosis. Herein, we summarize the cytogenetic features found in the the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer for t(16;21) in AML, as well as review the current literature associated with t(16;21), AML and its features.
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PMID:A t(16;21)(p11;q22) in Acute Myeloid Leukemia (AML) Resulting in Fusion of the FUS/TLS and ERG Genes: A Review of the Literature. 2718 48