Project description:Glioblastoma (GB) is the most aggressive form of glioma and is characterized by a poor prognosis and high recurrence, despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB, we performed differential methylation analysis between low and high-grade gliomas by using Infinium MethylationEPIC beadchips.
Project description:Bisulfite and oxidative bisulfite treated sample methylation analysis of IDH1 mutant and wild-type high grade human gliomas, to profile 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Genomic DNA isolated directly from fresh-frozen human high grade glioma specimens.
Project description:Glioma CIMP (G-CIMP) is a powerful determinant of tumor pathogenicity but the molecular cause of G-CIMP is a fundamental question that is unresolved. Here, we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), directly causes the G-CIMP in gliomas by remodeling the methylome.
Project description:Genome wide DNA methylation profiling of 112 human glioma samples. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in glioma samples, including 55 WHO grade 2 glioma samples, 33 WHO grade 3 glioma samples and 24 WHO grade 4 glioma samples.
Project description:Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array profiling of 20 primary, multi-region high-grade glioma samples. Total RNA was extracted from primary high-grade glioma samples and hybridized to GeneChip® Human Genome U133 Plus 2.0 Array according to the manufacturer's instructions.
Project description:To assess whether specific genes have relevant somatic genetic or epigenetic alterations in ectopic tissue, we used a combined analysis of transcriptome (confirmed by qRT-PCR on 68 genes), methylome, structural genome variations (copy number variants, CNVs) and miRNA profile of ectopic compared with orthotopic thyroids.
Project description:The cell and tissue of origin of high grade serous ovarian cancer (HGSC) is controversial. While the disease was traditionally assumed to arise from the ovarian surface epithelium (OSE), recent work supports an alternative model implicating the fallopian tube fimbriae epithelium (FTE). We used comparative DNA methylome analyses as a means to test these two competing models, hypothesizing that the HGSC methylome should more closely resemble its tissue of origin. Using two separate analysis methods, analysis within distinct genomic contexts, and validation studies using large-scale publically available HGSC methylome data, we consistently observed that the DNA methylome of HGSC more closely resembles FTE than OSE. These data support the FTE origin model, and suggest DNA methylome analysis as a useful approach to examine cell/tissue lineage origin in cancer. HGSC is the most common and lethal form of epithelial ovarian cancer (EOC). Two distinct tissues have been hypothesized as the tissue of origin of HGSC: OSE and FTE. We hypothesized that the DNA methylome of HGSC would more closely resemble the methylome of its tissue of origin. To test this, we profiled HGSC (n=10), OSE (n=7), and FTE (n=7) primary fresh-frozen tissues, and analyzed DNA methylome using Illumina 450K arrays (n=24) and Agilent Sure Select methyl-seq (n=7). We compared methylomes using statistical analyses of differentially methylated CpG sites (DMC) and differentially methylated regions (DMR), and methylation within a variety of different genomic contexts, including CpG island shores. We also analyzed methylation specifically at Homeobox (HOX) genes, due to their role in tissue specification. We used publically available HGSC methylome data (n=628) to provide additional comparison with FTE and OSE and potential validation. This analysis revealed that HGSC and FTE methylomes were significantly and consistently more highly conserved than were HGSC and OSE. Pearson correlations and hierarchal clustering of genes, promoters, CpG islands, CpG island shores, and HOX genes all revealed the increased relatedness of HGSC and FTE methylomes. In addition, two different large data sets of publically-available HGSC methylome data confirmed these relationships. In summary, our findings support the FTE origin model for HGSC, the most common and deadly EOC subtype. Due to its tissue-specificity and biochemical stability, interrogation of the DNA methylome appears to be a valuable approach to examine cell/tissue lineage in cancer.
