Project description:Purpose Accumulating evidence indicates aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. In this study, we have performed a wide DNA methylation study of a series of oral lichenoid disease in order to assess the relevance of DNA methylation changes in this premalignant disorder. Experimental Design Discovery phase utilized HumanMethylation27 DNA Analysis BeadChip assay in 18 OLD and 5 control samples. The differently methylated loci and the global DNA methylation surrogate LINE-, were further validated in an independent sample set consisting in 158 OLD and 65 controls. Results DNA methylation profile of the OLD showed only minor significant differences when compared to controls. MGC40178, ADORA1 and LINE-1 were slightly hypomethylated in 23, 40 and 43 % of the OLD samples respectively, while only in 13, 18 and 15% of the controls. Conclusions In summary, our data indicates that the frequency of aberrant DNA alteration is very low in OLD, which support the low rate of malignization of this oral potentially malignant disorder. Bisulphite converted DNA from the 17 Oral lichenoid samples and 5 control samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.217
Project description:Purpose: Accumulating evidence indicates aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. In this study, we have performed a wide DNA methylation study of a series of oral lichenoid disease in order to assess the relevance of DNA methylation changes in this premalignant disorder. Experimental Design: Discovery phase utilized the Illumina Golden Gate Cancer Panel I in 51 OLD and 6 control samples. The differently methylated loci and the global DNA methylation surrogate LINE-1, were further validated in an independent sample set consisting in 160 OLD and 65 controls. Results: DNA methylation profiles of the OLD showed only minor significant differences when compared to controls. Conclusions: In summary, our data indicates that the frequency of aberrant DNA alteration is very low in OLD, which support the low rate of malignization of this oral potentially malignant disorder. Bisulphite-converted DNA from the 51 oral lichenoid disease samples and 6 control samples were hybridised to the Illumina GoldenGate Methylation Cancer Panel I.
Project description:Analysis of serum starved prelamin A-accumulating hMSCs at gene expression level. The hypothesis tested in the present study was that prelamin A accumulation induces the dysregulation of genes that are essensial for cell survival under a stress condition such as serum starvation. The results provide important information about these genes and the functional categories that are dysregulated due to prelamin A accumulation in serum starved hMSCs. Two samples are analyzed in this microarray experiment: human mesenchymal stem cell cultured under serum starvation conditions (during 24 hours) which accumulate prelamin A (pre-hMSCs) and control mesenchymal stem cells (ctrl-hMSCs). 2 biological replicates (hMSCs derived from 2 different bone marrow donors) and 1 technical replicate are included in this analysis.
Project description:Human papillomavirus (HPV)-associated head and neck cancers (HNSCCs) have a distinct risk profile and appreciate a prognostic advantage compared to HPV-negative HNSCC. Promoter hypermethylation has been widely recognized as an important mechanism in the progression of HNSCC, but the extent to which this mechanism is consistent between HPV(+) and HPV(-) tumors is unknown. To assess the genome-wide methylation changes in HPV(+) and HPV(-) tumors, we analyzed DNA methylation and expression patterns in two HPV(+) and two HPV(-) cell lines. HPV(+) tumors have overall higher DNA methylation in genic and LINE1 regions than HPV(-) tumors, and polycomb repressive complex 2 (PRC2) targets tend to be much more highly methylated in HPV(+) cells. Bisulphite-converted DNA from 4 squamous cell carcinoma (SCC) cell lines were hybridized to the Illumina Infinium 27k Human Methylation Beadchip.
Project description:To broaden our understanding of the gene expression common to volar skin, we biopsied the dorsum of the hand, palm, dorsum of the foot and sole and collected DNA for methylation chip anlayses Total of 12 skin biopsy samples with 3 repeats from distinct individuals of each site: dorsum of hand, palm, dorstum of foot and sole. The samples below represent methylation data only.
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | Transcriptome analysis led to the unsupervised classification of carcinomas in two groups, associated with different outcomes {de Reynies, 2009 ; Giordano, 2009}. Subsequently, we have shown that unsupervised clustering further classified the tumors of the poor prognosis group in three different subgroups, two of them harbouring a cardinal molecular alteration {Ragazzon, 2010}. One is associated with p53 inactivation, the second with ?-catenin activation. No molecular defect has been identified in the third group so far. The aim is to describe the genome-wide methylome of adrenocortical tumors, and to assess the link with previously established molecular classifications. Experimental design: Genome-wide methylation patterns of 84 adenomas and 51 carcinomas were obtained with the Infinium HumanMethylation27 beadchip (Illumina). | Submitter : Olivia Barreau <olivia.barreau@inserm.fr> | Project leader : Jerome Bertherat <jerome.bertherat@inserm.fr>
Project description:DNA methylation profiling of airway epithelial cells (AECs) and peripheral blood mononuclear cells (PBMCs) from normal, atopic and asthmatic subjects. The Illumina GoldenGate Methylation Cancer Panel I was used to obtain DNA methylation profiles across approximately 1505 CpGs in AECs and PBMCs. Samples included 7 healthy, 9 atopic, 4 atopic asthmatic and 5 non-atopic asthmatic subjects. Please note that only some of the samples are matched (i.e. AECs and PBMCs from the same individual) due to DNA quality or sample collection (i.e. only one sample (AEC or PBMC) was collected from the patient). Bisulphite converted DNA from the 41 samples were hybridised to the Illumina GoldenGate Methylation Beadchip
Project description:Age-related changes in DNA methylation occurring in blood leukocytes during early childhood may reflect epigenetic maturation. We hypothesized that some of these changes involve gene networks of critical relevance in leukocyte biology and conducted a prospective study to elucidate the dynamics of DNA methylation. Serial blood samples were collected at 3, 6, 12, 24, 36, 48 and 60 months after birth in 10 healthy girls born in Finland and participating in the Type 1 Diabetes Prediction and Prevention Study. DNA methylation was measured using the HumanMethylation450 BeadChip. After filtering for the presence of polymorphisms and cell-lineage-specific signatures, 794 CpGs showed significant DNA methylation differences as a function of age in all children (41.5% age-methylated and 58.4% age-demethylated, bonferroni corrected p-value <0.001). Age-methylated CpGs were more frequently located in gene bodies and within +5 to +50 kilobases (kb) of transcription start sites (TSS), and enriched in developmental, neuronal and plasma membrane genes. Age-demethylated CpGs were associated to promoters and DNAse-I hypersensitivity sites, located within -5 to +5 kb of the nearest TSS, and enriched in genes related to immunity, antigen presentation, the polycomb-group protein complex and cytoplasm. This study reveals that susceptibility loci for complex inflammatory diseases (e.g. IRF5, NOD2, PTGER4) and genes encoding histone modifiers and chromatin remodeling factors (e.g. HDAC4, KDM2A, KDM2B, JARID2, ARID3A, SMARCD3) undergo DNA methylation changes in leukocytes during early childhood. These results open new perspectives to understand leukocyte maturation and provide a catalog of CpGs that may need to be corrected for age effects when performing DNA methylation studies in children. We analysed the longitudinal changes in DNA methylation in a total of 60 samples at 3, 6, 12, 24, 36, 48, and 60 months after birth, using serial DNA samples extracted from peripheral blood leukocytes of 10 healthy girls of the Diabetes Prediction and Prevention Study (DIPP).
Project description:The human glucocorticoid receptor (GRα) is overexpressed at the molecular and protein level in malignant human adrenocortical cancers. A stable cell line model of GRα overexpression was established using the H295R human adrenocortical cancer cell line. The following results were obtained from gene expression profiling of H295R_GRα and H295R_Control (empty vector) cells following treatment with either a GRα agonist (dexamethasone), GRα antagonist (RU486) or vehicle (ethanol) control. H295R_GRα and H295R_Control (empty vector) cells were treated in triplicate for 6 hours with dexamethasone 100 nM, RU486 100 nM or vehicle (ethanol) control.