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)

Specific gene mutations, loss of heterozygosity, deletions and/or amplifications of entire chromosomal regions and gene silencing have been described in gliomas. 82 samples from 81 patients were investigated to detect the deletion of TP53, RB1, CDKN2A genes, deletion of 1p36 and 19q13.3 region, amplification of EGFR gene, trisomy of chromosome 7 and monosomy of chromosome 10 in glial cells. Dual-colour interphase fluorescence in situ hybridization (I-FISH) with locus-specific and/or chromosome enumeration DNA probes were used for cytogenetic analyses. In the study, molecular cytogenetic analyses were successfully performed in 74 patients (91.3%) and were uninformative in 7 only (8.7%). The cytogenetic analyses were correlated with morphological data and clinical outcome. I-FISH was the essential part of diagnostics. In comparison with the clinical data, the patients' age seems to be a factor more important for the overall survival, rather than cytogenetic findings in glial tumours. The combined deletion of 1p36 and 19q13.3 chromosomal regions predicts longer overall survival for patients with oligodendroglial tumours.
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PMID:Cytogenetic analyses in 81 patients with brain gliomas: correlation with clinical outcome and morphological data. 1756 1

Anaplastic large cell lymphoma (ALCL) is a well-known entity, but there are no data on prognosis according to the age of the patient, especially in infants. A 2-month-old girl was admitted with a 2-week history of coughing, fever, and lymphadenopathy. Physical examination revealed mild respiratory distress, an erythematous macular rash on her trunk, massive cervical lymphadenopathy, splenomegaly, and very mild ascites. Chest radiograph showed bilateral pulmonary infiltrates, pleural effusion, and a mediastinal mass. CBC count showed WBC: 172,000/microL (PMN 40%, lymphocytes 47%, monocytes 3%); hemoglobin concentration: 8.7 g/dL; platelets: 390,000/microL. Cervical lymph node biopsy revealed anaplastic lymphoma with positive staining to ALK 1 and TIA 1. Immunophenotypic analysis of peripheral and bone marrow lymphoid cells showed an aberrant T-cell immunophenotype, including expression of CD3, CD45R0+, CD43+, and CD30+. Cytogenetic analysis performed on blood and bone marrow samples demonstrated the translocation t(2;5) (p23;q35), and trisomy 47. After leucophoresis, the child received chemotherapy according to the ALCL-99-EICNHL protocol, and was started on corticosteroids and cyclophosphamide, which resulted in marked improvement. After the second course, WBC decreased to 6000/microL without tumor lysis syndrome, but the child developed bacterial and fungal disseminated infections and died of septic shock with multiorgan failure. This report is of a rare case of infant anaplastic lymphoma and excellent response to treatment. Unfortunately, she did succumb to overwhelming infection. More reports of similar cases may determine the cause and prognosis of such children, helping to tailor therapy according to the age of the child and other prognostic factors, especially bone marrow involvement.
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PMID:Infant anaplastic lymphoma: case report and review of the literature. 1761 84

Oligodendroglial tumors presenting loss of heterozygosity (LOH) at 1p and 19q have been shown to be sensitive to chemotherapy, thus making 1p-19q status testing a key aspect in oligodendroglioma diagnosis and prognosis. Twenty-nine tumor samples (19 oligodendrogliomas, 10 oligoastrocytomas) were analyzed in order to obtain a molecular profile identifying those bearing 1p-19q LOH. Other genomic anomalies usually present in gliomas, such as EGFR amplification, CDKN2A/ARF deletion, 10q LOH and TP53 mutation, were also studied. Tumors with 1p-19q LOH overexpressed genes related to neurogenesis. Genes linked to immune response, proliferation and inflammation were overexpressed in the group with intact 1p-19q; this group could in turn be further divided in two subgroups: one overexpressing genes involved in immune response and inflammation that did not show major genetic aberrations other than the TP53 mutation and EGFR trisomy in a few cases, and another overexpressing genes related to immune response and proliferation that had a predominance of samples carrying several anomalies and presenting worse outcomes. This molecular signature was validated by analyzing a set of ten tumor samples (three oligodendrogliomas, seven oligoastrocytomas); all ten samples were correctly assigned. LOH at 1p-19q results in haploinsufficiency and copy number reduction of several genes, including NOTCH 2; this phenomenon produces a global change in gene expression inducing a pro-neural status that results in restrictions to cell migration and proliferation. Tumors without LOH at 1p-19q exhibit the opposite characteristics, explaining their more aggressive behavior.
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PMID:Loss of heterozygosity at 1p-19q induces a global change in oligodendroglial tumor gene expression. 1959 1

Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies in paediatric AML are scarce, and reported large differences in the frequency of MLL-PTD, frequently utilising mRNA RT-PCR only to detect MLL-PTDs. We studied the frequency of MLL-PTD in a large cohort of paediatric AML (n=276) and the results from two different methods, i.e. mRNA RT-PCR, and multiplex ligation-dependent probe amplification (MLPA), a method designed to detect copy number differences of specific DNA sequences. In some patients with an MLL-rearrangement, MLL-PTD transcripts were detected, but were not confirmed by DNA-MLPA, indicating that DNA-MLPA can more accurately detect MLL-PTD compared to mRNA RT-PCR. In paediatric AML, MLL-PTD was detected in 7/276 patients (2.5%). One case had a trisomy 11, while the others had normal cytogenetics. Furthermore 4 of the 7 patients revealed a FLT3-ITD, which was significantly higher compared with the other AML cases (p=0.016). In conclusion, using DNA-MLPA as a novel screenings technique in combination with mRNA RT-PCR a low frequency of MLL-PTD in paediatric AML was found. Larger prospective studies are needed to further define the prognostic relevance of MLL-PTD in paediatric AML.
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PMID:Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique. 2023 57

Despite the increasing knowledge about the genetic alterations and molecular pathways involved in gliomas, few studies have investigated the association between the gene expression profiles (GEP) and both cytogenetics and histopathology of gliomas. Here, we analyzed the GEP (U133Plus2.0 chip) of 40 gliomas (35 astrocytic tumors, 3 oligodendrogliomas, and 2 mixed tumors) and their association with tumor cytogenetics and histopathology. Unsupervised and supervised analyses showed significantly different GEP in low- vs high-grade gliomas, the most discriminating genes including genes involved in the regulation of cell proliferation, apoptosis, DNA repair, and signal transduction. In turn, among glioblastoma multiforme (GBM), 3 subgroups of tumors were identified according to their GEP, which were closely associated with the cytogenetic profile of their ancestral tumor cell clones: (i) EGFR amplification, (ii) isolated trisomy 7, and (iii) more complex karyotypes. In summary, our results show a clear association between the GEP of gliomas and tumor histopathology; additionally, among grade IV astrocytoma, GEP are significantly associated with the cytogenetic profile of the ancestral tumor cell clone. Further studies in larger series of patients are necessary to confirm our observations.
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PMID:Gene expression profiles of human glioblastomas are associated with both tumor cytogenetics and histopathology. 2048 45

Down syndrome (DS) associates with impaired brain functions, but the underlying mechanism(s) are yet unclear. The "gene dosage" hypothesis predicts that in DS, overexpression of a single gene can impair multiple brain functions through a signal amplification effect due to impaired regulatory mechanism(s). Here, we report findings attributing to impairments in the splicing process such a regulatory role. We have used DS fetal brain samples in search for initial evidence and employed engineered mice with MMU16 partial trisomy (Ts65Dn) or direct excess of the splicing-associated nuclear kinase Dyrk1A, overdosed in DS for further analyses. We present specific albeit modest changes in the DS brain's splicing machinery with subsequently amplified effects in target transcripts; and we demonstrate that engineered excess of Dyrk1A can largely recapitulate these changes. Specifically, in both the fetal DS brains and the Dyrk1A overdose models, we found ample modestly modified splicing-associated transcripts which apparently induced secondary enhancement in exon inclusion of key synaptic transcripts. Thus, DS-reduced levels of the dominant-negative TRKBT1 transcript, but not other TRKB mRNA transcripts, were accompanied by corresponding decreases in BDNF. In addition, the DS brains and Dyrk1A overdosage models showed selective changes in the transcripts composition of neuroligin mRNAs as well as reductions in the "synaptic" acetylcholinesterase variant AChE-S mRNA and corresponding increases in the stress-inducible AChE-R mRNA variant, yielding key synaptic proteins with unusual features. In cotransfected cells, Dyrk1A overdosage caused parallel changes in the splicing pattern of an AChE mini-gene, suggesting that Dyrk1A overdosage is both essential and sufficient to induce the observed change in the composition of AChE mRNA variants. Furthermore, the Dyrk1A overdosage animal models showed pronounced changes in the structure of neuronal nuclear speckles, where splicing events take place and in SR proteins phosphorylation known to be required for the splicing process. Together, our findings demonstrate DS-like brain splicing machinery malfunctioning in Dyrk1A overexpressing mice. Since individual splicing choices may alter cell fate determination, axon guidance, and synaptogenesis, these findings suggest the retrieval of balanced splicing as a goal for DS therapeutic manipulations early in DS development.
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PMID:Engineering DYRK1A overdosage yields Down syndrome-characteristic cortical splicing aberrations. 2060 Sep 7

Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and also to test new therapeutic approaches. The present study characterized cytogenetically PG-100, the first commercially available gastric cancer cell line derived from a Brazilian patient who had a gastric adenocarcinoma, using GTG banding and fluorescent in situ hybridization to determine MYC amplification. Twenty metaphases were karyotyped; 19 (95%) of them presented chromosome 8 trisomy, where the MYC gene is located, and 17 (85%) presented a deletion in the 17p region, where the TP53 is located. These are common findings for gastric carcinomas, validating PG100 as an experimental model for this neoplasia. Eighty-six percent of 200 cells analyzed by fluorescent in situ hybridization presented MYC overexpression. Less frequent findings, such as 5p deletions and trisomy 16, open new perspectives for the study of this tumor.
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PMID:Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line. 2065 94

The aim of this study was a cytogenetic analysis of stallions semen to find sex chromosome aberrations and to determine if there was an association between stallion's age and aberration frequency for the sex chromosomes. Sperm samples were collected from 22 stallions of various age from 3 to 23 years. Multicolour FISH was performed on each sample, using probes for the sex chromosomes and EGFR gene, localized on 4p12 in domestic horse. A total of 26199 sperm cells were analysed (from 1 070 to 1 532 per animal). Among the analysed cells, there were 50.318% with X chromosome, 48.543% with Y chromosome and 1.139% with aberrant chromosomes. The frequency of aberrations was: sex chromosomes nullisomy (0.466%), XY aneuploidy (0.454%), XX disomy (0.146%), YY disomy (0.041%), diploidy (0.024%) and trisomy XXY (0.008%). Additionally there was a correlation between the age of an animal and the frequency of sex chromosome aberration and a significant positive correlation between age and disomy of XY, XX, YY, trisomy of XXY, autosomal disomy was seen. A Correlation between the age of a stallion and the level of nullisomy was negative. The present study demonstrated that FISH technique is a powerful method to identify sex chromosome aberrations in equine spermatozoa and might be very helpful for a breeder during a selection for the best stallion.
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PMID:Determination of the correlation between stallion's age and number of sex chromosome aberrations in spermatozoa. 2132 52

Trisomy 11 (+11) as an isolated abnormality is a rare event in patients with acute myeloid leukemia (AML) and is associated with poor prognosis. We describe the clinicopathologic features of 18 AML patients with isolated +11 and their mutation status of NPM1, FLT3, NRAS ,KRAS, and KIT. Fourteen patients had de novo AML and 4 patients had a history of myelodysplastic syndrome (MDS). Fifteen patients had a progressive clinical course with refractory or relapsed disease. The median overall survival was 5 months (range, 2 to 48 months). Only 1 patient achieved complete remission after undergoing stem cell transplantation. The bone marrow median blast count was 65% (range, 22 to 86) and 14 patients had blasts >50%. The most common type of AML was AML without maturation (7 patients) classified by the World Health Organization classification system, or M1 (10 patients) by the French-American-British (FAB) system. FLT3 mutations were detected in 3 of 15 (20%) cases tested. RAS mutation was present in 1 of 16 (6%) cases and there was no evidence of NPM1 of KIT mutations (each tested in 12 cases). Our findings confirm previous reports that isolated +11 is associated with a poor prognosis in patients with AML and tends to be associated with FAB-M1 morphologic features. No evidence of NPM1 or KIT mutations were identified.
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PMID:Trisomy 11 as an isolated abnormality in acute myeloid leukemia is associated with unfavorable prognosis but not with an NPM1 or KIT mutation. 2157 23

Larger imbalances on chromosome 4p in the form of deletions associated with Wolf-Hirschhorn syndrome (WHS) and duplications of chromosome 4p have a defined clinical phenotype. The critical region for both these clinical disorders has been narrowed based on the genotype-phenotype correlations. However, cryptic rearrangements in this region have been reported infrequently. We report on a male patient with a microduplication of chromosome 4p, who presents with findings of macrocephaly, irregular iris pigmentation-heterochromia, and preserved linear growth in addition to overlapping features of trisomy 4p such as seizures, delayed psychomotor development, and dysmorphic features including prominent glabella, low-set ears, and short neck. Using a high-density oligonucleotide microarray, we have identified a novel submicroscopic duplication involving dosage sensitive genes TACC3, FGFR3, and LETM1. The microduplication did not involve WHSC1 and WHSC2 which are considered in the critical region for WHS and trisomy 4p. This patient's presentation and genomic findings help further delineate clinical significance of re-arrangements in the 4p16 region without the involvement of WHS critical region.
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PMID:A novel 4p16.3 microduplication distal to WHSC1 and WHSC2 characterized by oligonucleotide array with new phenotypic features. 2181 51


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