Project description:This SuperSeries is composed of the following subset Series: GSE25083: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: normal head and neck tissue GSE25089: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: HNSCC GSE25091: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: blood controls Refer to individual Series
Project description:Rap1GAP is a critical tumor suppressor gene that is down-regulated in multiple aggressive cancers such as head and neck squamous cell carcinoma, melanoma and pancreatic cancer. However, the mechanistic basis of rap1GAP down-regulation in cancers is poorly understood. By employing an integrative approach, we demonstrate polycomb-mediated repression of rap1GAP that involves EZH2, a histone methyltransferase in head and neck cancers. We further concomitant down-regulation of rap1GAP in head and neck cancers. EZH2 represses rap1GAP by facilitating the trimethylation of H3K27, a mark of gene repression, and also hypermethylation of rap1GAP promoter. These results provide a conceptual framework involving a microRNA-oncogene-tumor suppressor axis to understand head and neck cancer progression. OSCC3-siRNA Non-Targeting Vs. siRNA EZH2 with dye-swap, HOK-Adeno CMV Vs. Adeno EZH2.
Project description:Rap1GAP is a critical tumor suppressor gene that is down-regulated in multiple aggressive cancers such as head and neck squamous cell carcinoma, melanoma and pancreatic cancer. However, the mechanistic basis of rap1GAP down-regulation in cancers is poorly understood. By employing an integrative approach, we demonstrate polycomb-mediated repression of rap1GAP that involves EZH2, a histone methyltransferase in head and neck cancers. We further concomitant down-regulation of rap1GAP in head and neck cancers. EZH2 represses rap1GAP by facilitating the trimethylation of H3K27, a mark of gene repression, and also hypermethylation of rap1GAP promoter. These results provide a conceptual framework involving a microRNA-oncogene-tumor suppressor axis to understand head and neck cancer progression.
Project description:Patients with head and neck squamous cell carcinoma (HNSCC) have a poor prognosis due to the development of locoregional recurrences, distant metastases and second primary tumors. There is an urgent need for biomarkers that enable detection and monitoring of the disease to provide adequate therapeutic strategies. In this study we have investigated markers in peripheral blood cells (PBC) of 28 HNSCC patients who underwent surgery by means of expression profiling. Our hypothesis is that nucleated blood cells circulate continuously, also passing the tumor, and might change their expression profiles in response to tumor cell factors. For comparison, we enrolled a control group of 11 patients who underwent surgery in the head and neck region for non-HNSCC reasons. A set of 2,349 genes was found to be statistically different between the groups (p<0.05, false discovery rate-corrected) and the most prominently different pathways were EIF2 and mTOR signaling. These preliminary results are promising and warrant further studies on the definitive role of PBC gene expression as a biomarker for HNSCC detection and monitoring. Two-color experiment with each individual sample in a single channel. RNA of nucleated blood cells of humans was analysed. Case-control analysis, with 28 cases, patients with head and neck squamous cell carcinoma and 11 controls, without squamous cell carcinoma
Project description:Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas. The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples. Bisulphite-converted DNA from the 18 normal head and neck samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.
Project description:Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas (HNSCCs). The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples. Bisulphite-converted DNA from the 91 head and neck squamous cell carcinoma samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.
Project description:Using the Illumina EPIC array to measure DNAm of gMDSCs and neutrophils from diverse neonatal and adult blood sources, we found 189 differentially methylated CpGs between gMDSCs and neutrophils with a core of ten differentially methylated CpGs that were consistent across both sources of cells. Genes associated with these loci that are involved in immune responses include VCL, FATS, YAP1, KREMEN2, UBTF, MCC-1, and EFCC1. In two cancer patient groups that reflected those used to develop the methylation markers (head and neck squamous cell carcinoma (HNSCC) and glioma), all of the CpG loci were differentially methylated, reaching statistical significance in glioma cases and controls, while one was significantly different in the smaller HNSCC group. Our findings indicate that gMDSCs have a core of distinct DNAm alterations, informing future research on gMDSC differentiation and function.