Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • DISEASE  (2)
  • PROGRESSION  (2)
  • 1
    Keywords: CANCER ; EXPRESSION ; GROWTH ; tumor ; CELL ; MODEL ; PATHWAY ; PATHWAYS ; COHORT ; DISEASE ; GENE ; GENE-EXPRESSION ; RNA ; DIFFERENTIATION ; TUMORS ; ACTIVATION ; BINDING ; BIOLOGY ; TARGET ; CHROMATIN ; gene expression ; PROMOTER ; genetics ; MODULATION ; C-MYC ; REPRESSION ; TRANSCRIPTIONAL REPRESSION ; MYCN ; neuroblastoma ; N-MYC ; signaling ; ONCOLOGY ; B-CELL LYMPHOMAS ; miRNA ; outcome ; MICRORNA ; CELL BIOLOGY ; Genetic ; COHORTS ; EXPRESSION SIGNATURES ; PATHWAY DEREGULATION
    Abstract: Increased activity of MYC protein-family members is a common feature in many cancers. Using neuroblastoma as a tumor model, we established a microRNA (miRNA) signature for activated MYCN/c-MYC signaling in two independent primary neuroblastoma tumor cohorts and provide evidence that c-MYC and MYCN have overlapping functions. On the basis of an integrated approach including miRNA and messenger RNA (mRNA) gene expression data we show that miRNA activation contributes to widespread mRNA repression, both in c-MYC- and MYCN-activated tumors. c-MYC/MYCN-induced miRNA activation was shown to be dependent on c-MYC/MYCN promoter binding as evidenced by chromatin immunoprecipitation. Finally, we show that pathways, repressed through c-MYC/MYCN miRNA activation, are highly correlated to tumor aggressiveness and are conserved across different tumor entities suggesting that c-MYC/MYCN activate a core set of miRNAs for cooperative repression of common transcriptional programs related to disease aggressiveness. Our results uncover a widespread correlation between miRNA activation and c-MYC/MYCN-mediated coding gene expression modulation and further substantiate the overlapping functions of c-MYC and MYCN in the process of tumorigenesis. Oncogene (2010) 29, 1394-1404; doi:10.1038/onc.2009.429; published online 30 November 2009
    Type of Publication: Journal article published
    PubMed ID: 19946337
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: STAGE ; PROGRESSION ; AMPLIFICATION ; chemotherapy ; DELETIONS ; SPONTANEOUS REGRESSION ; PREDICTION ; pathology ; N-MYC ; EXPRESSION-BASED CLASSIFICATION
    Abstract: Purpose: To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression-based classification and established prognostic markers. Material and Methods: Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4x44K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n=634) by Kaplan-Meier estimates and Cox regression analyses. Results: The best-performing classifier predicted patient outcome with an accuracy of 0.95 (sensitivity 0.93, specificity 0.97) in the validation cohort. The highest potential clinical value of this predictor was observed for current low-risk patients (LR: 5-year EFS 0.84+/-0.02 vs 0.29+/-0.10; 5-year OS 0.99+/-0.01vs 0.76+/-0.11; both p〈0.001) and intermediate-risk patients (IR: 5-year EFS 0.88+/-0.06 vs 0.41+/-0.10; 5-year OS 1.0 vs 0.70+/-0.09; both p〈0.001). In multivariate Cox regression models for LR/IR patients the classifier outperformed risk assessment of the current German trial NB2004 (EFS: HR 5.07, 95%-CI 3.20-8.02, OS: HR 25.54, 95%-CI 8.40-77.66; both p〈0.001). Based on these findings, we propose to integrate the classifier into a revised risk stratification system for LR/IR patients. According to this system, we identified novel subgroups with poor outcome (5-year EFS 0.19+/-0.08; 5-year OS 0.59+/-0.1), for whom we propose intensified treatment, and with beneficial outcome (5-year EFS 0.87+/-0.05; 5-year OS 1.0), who may benefit from treatment de-escalation. Conclusion: Combination of gene expression-based classification and established prognostic markers improves risk estimation of LR/IR neuroblastoma patients. We propose to implement our revised treatment stratification system in a prospective clinical trial.
    Type of Publication: Journal article published
    PubMed ID: 25231397
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: APOPTOSIS ; CANCER ; SUSCEPTIBILITY ; PROGRESSION ; CELL-LINE ; p53 ; CASPASE-8 ; chemosensitivity ; GENOTYPE ; MDM2 SNP309
    Abstract: Background: Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients. The identification of single nucleotide polymorphisms (SNPs) may help explain the heterogeneity of neuroblastoma and assist in identifying patients at higher risk for poor survival. SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer. Of note, less than 2% of neuroblastoma tumors have a TP53 mutation at diagnosis. Patients and Methods: We selected 21 of the most frequently studied SNPs in the TP53 pathway and evaluated their association with outcome in 500 neuroblastoma patients using TaqMan allelic discrimination assays. Results and Conclusion: We investigated the impact of 21 SNPs on overall survival, event-free survival, age at diagnosis, MYCN status, and stage of the disease in 500 neuroblastoma patients. A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.
    Type of Publication: Journal article published
    PubMed ID: 25502557
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: EXPRESSION ; SURVIVAL ; Germany ; MODEL ; MODELS ; CLASSIFICATION ; DIAGNOSIS ; COHORT ; DEATH ; DISEASE ; MORTALITY ; RISK ; GENE ; GENE-EXPRESSION ; microarray ; PATIENT ; MARKER ; IMPACT ; STAGE ; AMPLIFICATION ; gene expression ; microarrays ; AGE ; MARKERS ; HIGH-RISK ; STRATEGIES ; SPONTANEOUS REGRESSION ; PREDICTION ; INFANTS ; pathology ; CHILDREN ; MICROARRAY ANALYSIS ; neuroblastoma ; ONCOLOGY ; REGRESSION ; overall survival ; INDEPENDENT PROGNOSTIC MARKER ; methods ; PROGNOSTIC MARKER ; PROFILES ; EXPRESSION PROFILES ; RISK STRATIFICATION ; SUBGROUPS ; MYC ; PROFILE ; outcome ; STRATEGY ; CONTRIBUTE ; COHORTS ; COX REGRESSION ; clinical oncology ; STRATIFICATION ; prognostic
    Abstract: Purpose To evaluate the impact of a predefined gene expression - based classifier for clinical risk estimation and cytotoxic treatment decision making in neuroblastoma patients. Patients and Methods Gene expression profiles of 440 internationally collected neuroblastoma specimens were investigated by microarray analysis, 125 of which were examined prospectively. Patients were classified as either favorable or unfavorable by a 144- gene prediction analysis for microarrays (PAM) classifier established previously on a separate set of 77 patients. PAM classification results were compared with those of current prognostic markers and risk estimation strategies. Results The PAM classifier reliably distinguished patients with contrasting clinical courses (favorable [n = 249] and unfavorable [n = 191]; 5- year event free survival [EFS] 0.84 +/- 0.03 v 0.38 +/- 0.04; 5-year overall survival [OS] 0.98 +/- 0.01 v 0.56 +/- 0.05, respectively; both P = .001). Moreover, patients with divergent outcome were robustly discriminated in both German and international cohorts and in prospectively analyzed samples (P = .001 for both EFS and OS for each). In subgroups with clinical low-, intermediate-, and high-risk of death from disease, the PAM predictor significantly separated patients with divergent outcome (low-risk 5-year OS: 1.0 v 0.75 +/- 0.10, P = .001; intermediaterisk: 1.0 v 0.82 +/- 0.08, P = .042; and high-risk: 0.81 +/- 0.08 v 0.43 = 0.05, P=.001). In multivariate Cox regression models based on both EFS and OS, PAM was a significant independent prognostic marker (EFS: hazard ratio [HR], 3.375; 95% CI, 2.075 to 5.492; P=.001; OS: HR, 11.119, 95% CI, 2.487 to 49.701; P=.001). The highest potential clinical impact of the classifier was observed in patients currently considered as non - high- risk (n= 289; 5- year EFS: 0.87= 0.02 v 0.44= 0.07; 5- year OS: 1.0 v 0.80= 0.06; both P=.001). Conclusion Gene expression - based classification using the 144- gene PAM predictor can contribute to improved treatment stratification of neuroblastoma patients
    Type of Publication: Journal article published
    PubMed ID: 20567016
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...