Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
Filter
  • RISK  (15)
Collection
Keywords
  • 1
    Keywords: APOPTOSIS ; CANCER ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; SURVIVAL ; tumor ; carcinoma ; CELL ; Germany ; PATHWAY ; DIAGNOSIS ; RISK ; GENE ; GENES ; SAMPLE ; SAMPLES ; PATIENT ; DNA ; MARKER ; RISK-FACTORS ; CELL-LINES ; DOWN-REGULATION ; EXPRESSION ANALYSIS ; ASSAY ; risk factors ; RATES ; CELL-LINE ; DNA methylation ; MARKERS ; SIGNALING PATHWAY ; HOMOLOG ; BETA ; HEAD ; squamous cell carcinoma ; GROWTH-FACTOR-BETA ; OVEREXPRESSION ; HYPOXIA ; NECK-CANCER ; signaling ; CELL CARCINOMA ; ONCOLOGY ; RE ; TUMOR-SUPPRESSOR ; TUMORIGENESIS ; CANDIDATE GENES ; TRANSPORTER ; analysis ; SUPPRESSOR ; USA ; CANDIDATE ; cancer research ; RISK-FACTOR ; CANCERS ; B-CELL ; DNA-METHYLATION ; modification ; tumor suppressor ; epigenetic
    Abstract: Head and neck squamous cell carcinoma (HNSCC) is a very aggressive cancer. In advanced stages, the patient has poor chances of receiving effective treatment, and survival rates are low. To facilitate timely diagnosis and improve treatment, elucidation of early detection markers is crucial. DNA methylation markers are particularly advantageous because DNA methylation is an early event in tumorigenesis, and the epigenetic modification, 5-methylcytosine, is a stable mark. A genome-wide screen using Restriction Landmark Genomic Scanning found a set of genes that are most commonly methylated in head and neck cancers. Five candidate genes: septin 9 (SEPT9), sodium-coupled monocarboxylate transporter 1 (SLM8), functional smad-suppressing element on chromosome 18 (FUSSEL18), early B-cell factor 3 (EBF3), and iroquois homeobox 1 (IRX1) were methylated in 27% to 67% of the HNSCC patient samples tested. Furthermore, similar to 50% of the methylated tumor samples shared methylation between two of the five genes (most commonly between EBF3 and IRX-1), and 15% shared methylation between three of the five genes. Expression analysis revealed candidate gene down-regulation in 25% to 93% of the HNSCC samples, and 5-aza-2'-deoxycytidine treatment was able to restore expression in at least 2 of 5 HNSCC cell lines for all of the genes tested. Overexpression of the three most frequently down-regulated candidates, SLC5A8, IRX1, and EBF3, validated their tumor suppressor potential by growth curve analysis and colony formation assay. Interestingly, all of the candidates identified may be involved in the transforming growth factor beta signaling pathway, which is often disrupted in HNSCC
    Type of Publication: Journal article published
    PubMed ID: 18559491
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: Germany ; RISK ; RISK-FACTORS ; risk factors ; leukemia ; histone deacetylase inhibitor ; DE-NOVO METHYLATION ; ACUTE PROMYELOCYTIC LEUKEMIA ; NORMAL CYTOGENETICS ; TRANS-RETINOIC ACID ; ONCOLOGY ; review ; RE ; USA ; EPIGENETICS ; CPG-ISLAND METHYLATION ; RISK-FACTOR ; MYELODYSPLASTIC SYNDROMES ; epigenetic ; PML-RAR-ALPHA ; DNA METHYLTRANSFERASE GENE ; PARTIAL TANDEM DUPLICATION
    Type of Publication: Journal article published
    PubMed ID: 18692688
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: LUNG-CANCER ; DISEASE ; RISK ; GENES ; GENOME ; SEQUENCE ; MASS-SPECTROMETRY ; NICOTINIC ACETYLCHOLINE-RECEPTORS ; CANCER SUSCEPTIBILITY LOCUS ; 15Q25.1
    Abstract: Genome-wide association studies have highlighted three major lung cancer susceptibility regions at 15q25.1, 5p15.33 and 6p21.33. To gain insight into the possible mechanistic relevance of the genes in these regions, we investigated the regulation of candidate susceptibility gene expression by epigenetic alterations in healthy and lung tumor tissues. For genes up or downregulated in lung tumors, the influence of genetic variants on DNA methylation was investigated and in vitro studies were performed. We analyzed 394 CpG units within 19 CpG islands in the susceptibility regions in a screening set of 34 patients. Significant findings were validated in an independent patient set (n=50) with available DNA and RNA. The most consistent overall DNA methylation difference between tumor and adjacent normal tissue on 15q25 was tumor hypomethylation in the promoter region of CHRNB4 with a median difference of 8% (P〈0.001), which resulted in overexpression of the transcript in tumors (P〈0.001). Confirming previous studies, we also found hypermethylation in CHRNA3 and telomerase reverse transcriptase (TERT) with significant expression changes. Decitabine treatment of H1299 cells resulted in reduced methylation levels in gene promoters, elevated transcript levels of CHRNB4 and CHRNA3, and a slight downregulation of TERT demonstrating epigenetic regulation of lung cancer cells. Single-nucleotide polymorphisms rs421629 on 5p15.33 and rs1948, rs660652, rs8040868 and rs2036527 on 15q25.1, previously identified as lung cancer risk or nicotine-addiction modifiers, were associated with tumor DNA methylation levels in the promoters of TERT and CHRNB4 (P〈0.001), respectively, in two independent sample sets (n=82; n=150). In addition, CHRNB4 knockdown in two different cell lines (A549 and H1299) resulted in reduced proliferation (P(A549)〈0.05;P(H1299)〈0.001) and propensity to form colonies in H1299 cells. These results suggest epigenetic deregulation of nicotinic acetylcholine receptor subunit (nAChR) genes which in the case of CHRNB4 is strongly associated with genetic lung cancer susceptibility variants and a functional impact on tumorigenic potential.Oncogene advance online publication, 3 September 2012; doi:10.1038/onc.2012.344.
    Type of Publication: Journal article published
    PubMed ID: 22945651
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: RISK ; VARIANTS ; BREAST ; COLORECTAL-CANCER ; TRAITS ; MYC ; GENOME-WIDE ASSOCIATION ; ENHANCERS ; GERMLINE EPIMUTATION ; HUMAN GENE-EXPRESSION ; LONG-RANGE INTERACTION
    Type of Publication: Journal article published
    PubMed ID: 21614091
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: CANCER ; RISK ; DNA methylation ; HYPERMETHYLATION ; OLDER PATIENTS ; PROGNOSTIC IMPACT ; AML ; ISLANDS ; MICRORNA-EXPRESSION SIGNATURES ; DNMT3A MUTATIONS
    Abstract: Purpose Molecular risk stratification of acute myeloid leukemia (AML) is largely based on genetic markers. However, epigenetic changes, including DNA methylation, deregulate gene expression and may also have prognostic impact. We evaluated the clinical relevance of integrating DNA methylation and genetic information in AML. Methods Next-generation sequencing analysis of methylated DNA identified differentially methylated regions (DMRs) associated with prognostic mutations in older ( 60 years) cytogenetically normal (CN) patients with AML (n = 134). Genes with promoter DMRs and expression levels significantly associated with outcome were used to compute a prognostic gene expression weighted summary score that was tested and validated in four independent patient sets (n = 355). Results In the training set, we identified seven genes (CD34, RHOC, SCRN1, F2RL1, FAM92A1, MIR155HG, and VWA8) with promoter DMRs and expression associated with overall survival (OS; P .001). Each gene had high DMR methylation and lower expression, which were associated with better outcome. A weighted summary expression score of the seven gene expression levels was computed. A low score was associated with a higher complete remission (CR) rate and longer disease-free survival and OS (P 〈 .001 for all end points). This was validated in multivariable models and in two younger (〈 60 years) and two older independent sets of patients with CN-AML. Considering the seven genes individually, the fewer the genes with high expression, the better the outcome. Younger and older patients with no genes or one gene with high expression had the best outcomes (CR rate, 94% and 87%, respectively; 3-year OS, 80% and 42%, respectively). Conclusion A seven-gene score encompassing epigenetic and genetic prognostic information identifies novel AML subsets that are meaningful for treatment guidance.
    Type of Publication: Journal article published
    PubMed ID: 24378410
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: CANCER ; EXPRESSION ; SURVIVAL ; tumor ; carcinoma ; CELL ; LUNG ; MODEL ; THERAPY ; CLASSIFICATION ; lung cancer ; LUNG-CANCER ; DEATH ; DISEASE ; RISK ; PROTEIN ; SAMPLE ; SAMPLES ; transcription ; TUMORS ; PATIENT ; DNA ; TRANSCRIPTION FACTOR ; BREAST-CANCER ; TARGET ; STAGE ; IDENTIFICATION ; PATTERNS ; METASTASIS ; chemotherapy ; DNA methylation ; HETEROZYGOSITY ; PROGNOSTIC-FACTORS ; MULTIVARIATE ; CARCINOMAS ; PROGNOSTIC FACTORS ; adenocarcinoma ; ADENOCARCINOMAS ; squamous cell carcinoma ; TARGETS ; METHYLATION ; PROGNOSTIC FACTOR ; staging ; protein expression ; RELATIVE RISK ; CELL CARCINOMA ; SUBSET ; PATTERN ; THERAPIES ; overall survival ; LIBRARIES ; PROGNOSTIC-FACTOR ; CPG ISLANDS ; LEVEL ; INTERVAL ; methods ; EXPRESSION PROFILES ; ADJUVANT CHEMOTHERAPY ; USA ; NSCLC ; genomic ; SQUAMOUS-CELL ; PREDICT ; MEDICINE ; nonsmall cell lung cancer ; correlates ; DNA-METHYLATION ; scanning ; LONG ARM ; SQUAMOUS-CELL-CARCINOMAS
    Abstract: Background Lung cancer is the leading cause of cancer-related death worldwide. Currently, tumor, node, metastasis (TNM) staging provides the most accurate prognostic parameter for patients with non-small cell lung cancer (NSCLC). However, the overall survival of patients with resectable tumors varies significantly, indicating the need for additional prognostic factors to better predict the outcome of the disease, particularly within a given TNM subset. Methods and Findings In this study, we investigated whether adenocarcinomas and squamous cell carcinomas could be differentiated based on their global aberrant DNA methylation patterns. We performed restriction landmark genomic scanning on 40 patient samples and identified 47 DNA methylation targets that together could distinguish the two lung cancer subgroups. The protein expression of one of those targets, oligodendrocyte transcription factor 1 (OLIG1), significantly correlated with survival in NSCLC patients, as shown by univariate and multivariate analyses. Furthermore, the hazard ratio for patients negative for OLIG1 protein was significantly higher than the one for those patients expressing the protein, even at low levels. Conclusions Multivariate analyses of our data confirmed that OLIG1 protein expression significantly correlates with overall survival in NSCLC patients, with a relative risk of 0.84 (95% confidence interval 0.77-0.91, p 〈 0.001) along with T and N stages, as indicated by a Cox proportional hazard model. Taken together, our results suggests that OLIG1 protein expression could be utilized as a novel prognostic factor, which could aid in deciding which NSCLC patients might benefit from more aggressive therapy. This is potentially of great significance, as the addition of postoperative adjuvant chemotherapy in T2N0 NSCLC patients is still controversial
    Type of Publication: Journal article published
    PubMed ID: 17388669
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: CANCER ; SURVIVAL ; tumor ; Germany ; LUNG ; CT ; DIAGNOSIS ; INFORMATION ; lung cancer ; LUNG-CANCER ; TOOL ; DEATH ; EPIDEMIOLOGY ; RISK ; GENE ; GENES ; GENOME ; EFFICIENCY ; TIME ; DNA ; MARKER ; RISK-FACTORS ; GENETIC POLYMORPHISMS ; BIOMARKERS ; BIOLOGY ; polymorphism ; POLYMORPHISMS ; FIELD ; BREAST-CANCER ; TARGET ; IDENTIFICATION ; LESIONS ; HEALTH ; ASSAY ; genetics ; CIGARETTE-SMOKING ; risk factors ; smoking ; PROSTATE-CANCER ; DNA methylation ; EFFICIENT ; MARKERS ; TUMOR-SUPPRESSOR GENE ; cancer risk ; HIGH-RISK ; genetic polymorphism ; TARGETS ; HISTONE DEACETYLASE ; non-small cell lung cancer ; BETA-CAROTENE ; ONCOLOGY ; RE ; genomics ; biomarker ; CANCER DEVELOPMENT ; methods ; ASSAYS ; HIGH-THROUGHPUT ; USA ; EPIGENETICS ; cancer research ; RISK-FACTOR ; CANCERS ; CANCER-RISK ; TOOLS ; FHIT GENE ; quantitative ; GENOME-WIDE ASSOCIATION ; modification ; POOLED-ANALYSIS ; MODIFIERS ; epigenetic ; ABERRANT PROMOTER METHYLATION
    Abstract: Lung cancer is the leading cause of cancer-related death and thus a major health problem. The efficiency of current treatment modalities for lung cancer depends strongly on the time of diagnosis, with better chances of survival if a tumor has been detected at an early stage. Thus, there is an urgent need for rapid and efficient early detection methods. Biomarkers represent a possible alternative to current, rather expensive, screening tools such as spiral computer tomography (CT), or may allow the identification of high risk groups for whom screening would be cost efficient. Although most lung cancers are the consequence of smoking, a substantial fraction of molecular-epidemiological studies point to high-prevalence, low-penctrance genetic polymorphisms as modifiers of environmental lung cancer risk. In the past the genomics field has also made significant advances in identifying genetic lesions that can now be harvested with the goal of identifying novel biomarkers for lung cancer. Furthermore, the importance of epigenetic changes that occur during lung cancer development has been reported, but has been underestimated in the past. Novel high-throughput, quantitative assays for the detection of DNA methylation or histone tail modifications are now applied, to search for alterations in the lung cancer genome and will identify novel cancer-related genes that may become attractive targets for treatment, provide new insight into the biology of lung cancers, and could also become useful biomarkers for the early detection of lung cancer in sputum, or may be used as prognostic markers. Thus, an integrative approach in lung cancer research combining epidemiological, genetic and epigenetic information becomes an important concept for the future. (C) 2008 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 18425819
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: CANCER ; CELLS ; tumor ; carcinoma ; CELL ; human ; RISK ; GENE ; GENES ; PROTEIN ; SAMPLE ; SAMPLES ; TIME ; PATIENT ; DNA ; MARKER ; primary ; CARCINOGENESIS ; CELL-LINES ; TARGET ; early detection ; IDENTIFICATION ; LESIONS ; NEOPLASIA ; ASSAY ; PROMOTER ; PROMOTERS ; cervical cancer ; CERVICAL-CANCER ; FUSION ; DNA methylation ; MARKERS ; TUMOR-SUPPRESSOR GENE ; FRAGMENTS ; PREDICTION ; SERIES ; FREQUENT ; TARGETS ; METHYLATION ; ONCOLOGY ; RE ; GENE PROMOTER ; CPG ISLANDS ; ASSAYS ; PROFILES ; PROMOTER HYPERMETHYLATION ; USA ; CPG ISLAND HYPERMETHYLATION ; cancer research ; CANCERS ; FRAGMENT ; SPECIMENS ; SET ; PROFILE ; GENE PROMOTERS ; lipoma ; ABERRANT METHYLATION ; CANCER PRECURSORS ; NUCLEOLAR PROTEIN
    Abstract: Aberrant methylation of CpG islands in gene promoters often represents an early clonal event in carcinogenesis. Accordingly, defining methylation profiles may be useful for developing marker panels for early detection or predicting the risk of cancer precursors. To identify specific genes frequently methylated in cervical cancer, we conducted methylation profiling of 20 primary human cervical cancers using NotI-based restriction landmark genomic scanning (RLGS). Of 2,172 RLGS fragments analyzed (average, 1,753 CpG islands per patient), 186 RLGS fragments were lost in at least one tumor and 40 were lost in three or more. Methylation was identified in 19 (95%) of 20 tumor samples compared with normal DNA. Bisulfite sequencing was conducted to confirm RLGS results. Of the confirmed markers frequently methylated, we developed Methylight assays for two corresponding genes, nucleolar protein 4 (NOL4), and lipoma HMGIC fusion partner-like protein 4 (LHFPL4), which were methylated in 85% and 55% of cancers, respectively. Using these assays, we further confirmed frequent CpG island methylation in the original cancers and in another independent series of 15 cervical cancers. We also showed methylation at a reduced frequency in a set of carefully reviewed cytology specimens demonstrating cells exfoliated from cancer precursor lesions. In summary, we identified, for the first time, NOL4 and LHFPL4 as novel methylation targets specific for cervical cancer. Inclusion of NOL4 and LHFPL4 in evaluating methylation panels for early detection, risk prediction, and etiologic research on cervical cancer is warranted
    Type of Publication: Journal article published
    PubMed ID: 18381458
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: CANCER ; CELLS ; SURVIVAL ; RISK ; TRANSPLANTATION ; leukemia ; PHENOTYPE ; CHILDREN ; CHRONIC MYELOGENOUS LEUKEMIA ; MYELODYSPLASTIC SYNDROME ; ACUTE MYELOID-LEUKEMIA ; RAS MUTATIONS ; RETROSPECTIVE ANALYSIS
    Abstract: Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of cancer, including myeloid leukemia. We hypothesized that CpG island hypermethylation also occurs in juvenile myelomonocytic leukemia (JMML) and investigated whether it is associated with clinical, hematologic, or prognostic features. Based on quantitative measurements of DNA methylation in 127 JMML cases using mass spectrometry (MassARRAY), we identified 4 gene CpG islands with frequent hypermethylation: BMP4 (36% of patients), CALCA (54%), CDKN2B (22%), and RARB (13%). Hypermethylation was significantly associated with poor prognosis: when the methylation data were transformed into prognostic scores using a LASSO Cox regression model, the 5-year overall survival was 0.41 for patients in the top tertile of scores versus 0.72 in the lowest score tertile (P = .002). Among patients given allogeneic hematopoietic stem cell transplantation, the 5-year cumulative incidence of relapse was 0.52 in the highest versus 0.10 in the lowest score tertile (P = .007). In multivariate models, DNA methylation retained prognostic value independently of other clinical risk factors. Longitudinal analyses indicated that some cases acquired a more extensively methylated phenotype at relapse. In conclusion, our data suggest that a high-methylation phenotype characterizes an aggressive biologic variant of JMML and is an important molecular predictor of outcome.
    Type of Publication: Journal article published
    PubMed ID: 21406719
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    facet.materialart.
    Unknown
    Cancer Treatment Reviews 37 (Suppl.1), S8-S12 
    Keywords: RISK ; GENE ; GENE-EXPRESSION ; GENOME ; DIFFERENTIATION ; C/EBP-ALPHA ; TUMOR-SUPPRESSOR ; ACUTE MYELOID-LEUKEMIA ; BINDING-PROTEIN-ALPHA ; miRNA ; SAGA COMPLEX ; HNRNP E2 ; MAMMALIAN DNA ; SINGLE CEBPA MUTATIONS
    Abstract: Epigenetic mechanisms synergize with genetic alterations in modulating gene expression patterns in cancer cells. While epigenetic alterations are reversible genetic modifications are not. This has raised the attention of many groups to focus on a better understanding of the molecular mechanisms that underlie the establishment of altered DNA methylation, histone modifications patterns and miRNA expression. The improved understanding of these mechanisms we will in turn allow us to improve the strategies that can be used for epigenetic therapies. In this review we will discuss and summarize briefly our current knowledge of epigenetic alterations in leukemias and will turn our attention to a concrete example of epigenetic deregulation of CCAAT/enhancer-binding protein alpha (C/EBP alpha), a key regulator for granulocytic differentiation of common myeloid progenitor cells in order to highlight the cooperativity of genetic and epigenetic mechanisms acting on this gene during the process of leukemogenesis.
    Type of Publication: Journal article published
    PubMed ID: 21601364
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...