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:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hodgkin's disease (HD) and Ki-1 positive anaplastic large cell lymphoma (Ki-1 ALCL) appear pathologically and immunohistochemically related, and a common histogenesis has been postulated in at least some cases. The breakpoints of the t(2;5) (p23;q35) [corrected] translocation, which is reported in about 40% of Ki-1 ALCL, have recently been cloned. They involve a novel tyrosine kinase gene, ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse transcriptase polymerase chain reaction (RT-PCR) using NPM and ALK primers consistently detects a fusion product in Ki-1 ALCL cases with the translocation. To determine if this tumor-specific genetic alteration also occurs in HD, we performed NPM-ALK RT-PCR on RNA samples extracted from 40 lymph node biopsies of HD (25 nodular sclerosis, 11 mixed cellularity, 2 lymphocyte depleted, 2 lymphocyte predominant). Using control samples, the sensitivity of the NPM-ALK RT-PCR assay was shown to be at least 1:10(4). Amplifiable template was confirmed in all samples by RT-PCR using beta-actin primers. None of the 40 cases showed the expected 177-bp RT-PCR product indicative of the translocation. We conclude that the most common primary genetic alteration in Ki-1 ALCL, the t(2;5), is absent or very infrequent in typical cases of HD. These results further support the concept that HD and Ki-1 ALCL are pathogenetically distinct entities.
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PMID:Reverse transcriptase polymerase chain reaction for the Ki-1 anaplastic large cell lymphoma-associated t(2;5) translocation in Hodgkin's disease. 752 17

Anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD) have some pathologic and immunohistochemical similarities, and a histogenetic relationship between them has been suggested by some investigators. By cytogenetic study, the t(2;5)(p23;q35) translocation appears to be unique for ALCL. The breakpoints of the t(2;5)(p23;q35) have recently been cloned and are reported to involve a novel tyrosine kinase gene, anaplastic lymphoma kinase (alk), on chromosome 2 and the nucleophosmin gene (npm) on chromosome 5. Therefore, we studied the frequency of npm-alk translocation in ALCL using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. We also studied HD and a variety of reactive lymphoid lesions since there is contradictory information in the literature on the occurrence of the npm-alk rearrangement in HD. We detected npm-alk hybrid mRNA in 8 of 22 cases of ALCL (36%), but none of the 21 cases of HD or the 11 cases with reactive lesions contained amplifiable template. All positive ALCL had the T or indeterminate phenotype and occurred in young adults or children. There was very good correlation between a cytogenetically detectable t(2;5) and a positive signal by RT-PCR. Our results indicate a selective but relatively infrequent association between the t(2;5) and ALCL of T or indeterminate phenotype, not shared with HD or reactive hyperplasia.
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PMID:Transcripts of the npm-alk fusion gene in anaplastic large cell lymphoma, Hodgkin's disease, and reactive lymphoid lesions. 757 58

The cytogenetics of Hodgkin's disease (HD) is poorly understood. However, a t(2;5) is a common finding in CD30+ anaplastic large cell lymphoma (ALCL), a neoplasm thought by some to be closely related to HD. Recently, the t(2;5) has been cloned and found to represent fusion of the NPM gene with the ALK gene. Using Southern blot hybridization, one group has reported finding rearrangements of NPM in a proportion of cases of both ALCL and HD. In the current study, we used a highly sensitive reverse transcriptase-polymerase chain reaction methodology to analyze 34 cases of HD for the t(2;5). We were unable to find polymerase chain reaction evidence for the t(2;5) in any of the cases of HD, a result significantly different from our previous study of CD30+ non-Hodgkin's lymphomas (P < .02) including ALCL (P < .04), using identical methods. Our results do not support the hypothesis that the t(2;5) represents a common chromosomal abnormality for both HD and ALCL.
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PMID:Absence of the t(2;5) in Hodgkin's disease. 749 2

CD30 positive anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin's lymphoma associated with a specific chromosome translocation between chromosomes 2 and 5. Recent molecular characterization of the translocation breakpoint has identified a gene fusion between NPM (nucleophosmin) and ALK (anaplastic lymphoma kinase). Using a DNA hybridization technique, the NPM rearrangement was found among 5/5 ALCL samples. We have developed a PCT methodology which has enabled the detection of the NPM-ALK rearrangements amongst seven t(2;5)(p23;q35) ALCL cases based on a long-range PCR of genomic DNA. The rapidity and robustness of this method may have diagnostic applications for ALCL.
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PMID:Detection of NPM-ALK DNA rearrangement in CD30 positive anaplastic large cell lymphoma. 777 31

Fifty-six cases of anaplastic large cell lymphoma (ALCL), 23 cases of Hodgkin's disease, and 16 cases of diffuse large cell lymphoma were investigated for the t(2;5)(p23;q35) translocation. The translocation was detected by using cytogenetic analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry with P80 antibody directed against the kinase domain of anaplastic lymphoma kinase (ALK) of the chimeric NPM/ALK protein. In all but three cases of ALCL, we found an agreement between cytogenetic analysis, RT-PCR, and P80 staining. However, in one case, the t(2;5) translocation was detected with cytogenetic analysis, but RT-PCR and P80 staining were found to be negative. Conversely, in another case the karyotype was normal, but the hybrid mRNA and P80 staining were found to be positive. In one case, malignant cells showed a translocation involving chromosomes 1q25 and 2p23 and were strongly positive for P80 staining. Such a result could be expected because P80 antibody detects the kinase domaine of the ALK protein encoded by chromosome 2p23. Overall 73.2% (41 of 56) of cases were found to be positive. However, the highest percentage (23 of 26 cases; 88.5%) of P80 positive cases was found in children compared with 60% (18 of 30 cases) in adult ALCL (P < .05). In Hodgkin's disease, Reed-Sternberg cells were found to be clearly negative by RT-PCR and with P80 antibody. The latter results suggest that Hodgkin's disease and t(2;5)-positive ALCL are distinct biological entities and that the demonstration of the t(2;5) translocation is of diagnostic importance in differentiating these two entities. The results of the present study indicate that immunohistochemistry with P80 antibody is a reliable method for detecting NPM/ALK chimeric protein.
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PMID:High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining. 854 53

The CD30+ anaplastic large cell lymphoma (ALCL) represents a new lymphoma entity thought to be related to Hodgkin'S disease (HD), but displaying also its own unique features. Cytogenetic studies of ALCL have demonstrated the presence of a (2;5)(p23;q35) translocation in a substantial number of these cases. Recently, the t(2;5) has been cloned and described to represent fusion of the NPM gene with the ALK gene on chromosome 5. To better define the spectrum of lymphomas containing this abnormality we have analyzed 50 continuous human cell lines established from various types of non-Hodgkin's lymphoma, ALCL and HD. In a first step, the expression of the NPM-ALK fusion gene was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). In a second step, the t(2;5)-carrying cells were tested for the translation of functional chimeric mRNA into a fusion protein by immuno-staining of single cells with a polyclonal antibody. The NPM-ALK fusion transcript and the p80 protein were detected in eight of nine ALCL cell lines. We were unable to find PCR evidence for the t(2;5) in any of the non-ALCL cell lines including other CD30+ cell lines. As all seven bona fide HD cell lines were NPM-ALK-negative, these results do not support the notion that the t(2;5) represents a chromosomal aberration common to both ALCL and HD.
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PMID:The (2;5)(p23;q35) translocation in cell lines derived from malignant lymphomas: absence of t(2;5) in Hodgkin-analogous cell lines. 855 20

The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT-PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.
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PMID:Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease. 856 33

The fusion gene NPM-ALK occurs in a subset of anaplastic large cell lymphomas (ALCLs), as a result of a chromosomal translocation, t(2;5) (p23;q35). It has been suggested that Hodgkin's disease (HD) and ALCL share a common histogenesis because of pathological and phenotypical similarities. In order to check this hypothesis, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to detect the hybrid NPM-ALK gene in 30 tumour samples, including 22 lymph node biopsies from HD and eight ALCL specimens. The threshold level of sensitivity was shown to reach at least 1/10(4) by dilution experiments using cell lines as positive and negative controls. The expected 177 bp product indicative of the NPM-ALK rearrangement was identified in Karpas 299 and SUDHL-1 cell lines and in two out of eight ALCLs. The 22 HD cases were negative, even after two successive tests. Thus, since the ALCL-specific genetic alteration was absent in our series of HD cases, the present study does not support the hypothesis that HD and ALCL are histogenetically related entities.
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PMID:Molecular analysis of the NPM-ALK rearrangement in Hodgkin's disease. 868 74

The breakpoints of the translocation t(2;5)(p23;q35) associated with Ki-1-positive anaplastic large cell lymphoma (Ki-1 ALCL) have recently been cloned. They involve a novel tyrosine kinase gene, ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse transcriptase-polymerase chain reaction (RT-PCR) with NPM and ALK primers detects a consistent fusion product in Ki-1 ALCL cases that have the translocation. In the course of a survey of 15 cases of Ki-1 ALCL, we identified a single case with a slightly smaller NPM-ALK RT-PCR product, among 12 cases positive for this fusion RNA. Sequencing of this novel NPM-ALK RT-PCR product showed an in-frame junction of NPM to ALK, 30 bases distal to the usual ALK junction site, but at the usual NPM Junction site. The predicted chimeric protein in this case is thus shorter by 10 amino acids, but the putative ALK catalytic domain remains intact. PCR with ALK primers bracketing the novel fusion point, performed on either cDNA or genomic DNA, yielded the same product, confirming that this novel ALK fusion point was located within an exon. Hybridization analysis of the genomic junction fragment isolated by long-range DNA PCR suggested that the ALK genomic breakpoint was also exonic. Cloning and sequencing of the genomic breakpoint confirmed that the break occurred within the 5' portion of the ALK exon participating in the fusion junction, 28 bases 3' to the normal ALK exon boundary, resulting in the use of a cryptic splice acceptor site two bases distal to the breakpoint. This case demonstrates that, in translocations resulting in chimeric transcripts, genomic breakpoints may rarely lie within an exon, provided that the reading frame is maintained and no domains presumed critical to tumorigenesis are deleted.
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PMID:Molecular variant of the NPM-ALK rearrangement of Ki-1 lymphoma involving a cryptic ALK splice site. 872 82

The breakpoints of the translocation t(2;5)(p23;q35) associated with Ki-1-positive anaplastic large-cell lymphoma (Ki-1 ALCL) involve a novel tyrosine kinase gene, ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse transcriptase-polymerase chain reaction (RT-PCR) using NPM and ALK primers detects a consistent fusion product in Ki-1 ALCL cases with the translocation, resulting from genomic breakpoints within the same respective introns of NPM and ALK. To examine the feasibility of long-range DNA PCR with the same exonic NPM and ALK primers for the detection of the genomic NPM-ALK rearrangement, we examined 20 cases of Ki-1 ALCL previously characterized by NPM-ALK RT-PCR. Ten cases were positive for the NPM-ALK fusion RNA and 10 were negative. We first confirmed that both the NPM and ALK normal introns are relatively short, approximately 1 and 2 kb, respectively, suggesting that the largest possible size for the chimeric NPM-ALK intron would be about 3 kb. All 10 cases positive by RT-PCR were also positive by long-range DNA PCR. The DNA PCR products ranged, as expected, from the sizes of the normal introns, between 0.5 and 2.5 kb. All 10 RT-PCR-negative cases were also negative by long-range DNA PCR, and control templates for RT-PCR and long-range DNA PCR were successfully amplified. Thus, we have shown that the introns involved by the NPM-ALK rearrangement seen in some Ki-1 lymphomas are relatively short, making the genomic rearrangement amenable to reliable detection by long-range DNA PCR. Furthermore, the variability observed in the sizes of chimeric introns in evidence against clustering of the genomic breakpoints within these introns.
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PMID:Detection of the NPM-ALK genomic rearrangement of Ki-1 lymphoma and isolation of the involved NPM and ALK introns. 886 27


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