van der Auwera I.,University of Antwerp |
Yu W.,Johns Hopkins University |
Suo L.,Johns Hopkins University |
van Neste L.,OncoMethylome science SA |
And 6 more authors.
PLoS ONE | Year: 2010
Background: Abnormal DNA methylation is well established for breast cancer and contributes to its progression by silencing tumor suppressor genes. DNA methylation profiling platforms might provide an alternative approach to expression microarrays for accurate breast tumor subtyping. We sought to determine whether the distinction of the inflammatory breast cancer (IBC) phenotype from the non-IBC phenotype by transcriptomics could be sustained by methylomics. Methodology/Principal Findings: We performed methylation profiling on a cohort of IBC (N = 19) and non-IBC (N = 43) samples using the Illumina Infinium Methylation Assay. These results were correlated with gene expression profiles. Methylation values allowed separation of breast tumor samples into high and low methylation groups. This separation was significantly related to DNMT3B mRNA levels. The high methylation group was enriched for breast tumor samples from patients with distant metastasis and poor prognosis, as predicted by the 70-gene prognostic signature. Furthermore, this tumor group tended to be enriched for IBC samples (54% vs. 24%) and samples with a high genomic grade index (67% vs. 38%). A set of 16 CpG loci (14 genes) correctly classified 97% of samples into the low or high methylation group. Differentially methylated genes appeared to be mainly related to focal adhesion, cytokine-cytokine receptor interactions, Wnt signaling pathway, chemokine signaling pathways and metabolic processes. Comparison of IBC with non-IBC led to the identification of only four differentially methylated genes (TJP3, MOGAT2, NTSR2 and AGT). A significant correlation between methylation values and gene expression was shown for 4,981 of 6,605 (75%) genes. Conclusions/Significance: A subset of clinical samples of breast cancer was characterized by high methylation levels, which coincided with increased DNMT3B expression. Furthermore, an association was observed with molecular signatures indicative of poor patient prognosis. The results of the current study also suggest that aberrant DNA methylation is not the main force driving the molecular biology of IBC. © 2010 Van der Auwera et al.
Bosch L.J.W.,VU University Amsterdam |
Mongera S.,VU University Amsterdam |
Droste J.S.T.S.,VU University Amsterdam |
Oort F.A.,VU University Amsterdam |
And 7 more authors.
Cellular Oncology | Year: 2012
Background Stool-based molecular tests hold large potential for improving colorectal cancer screening. Here, we investigated the analytical sensitivity of a DNA methylation assay on partial stool samples, and estimated the DNA degradation in stool over time. In addition, we explored the detection ofDNA methylation in fecal immunochemical test (FIT) fluid. Materials and Methods Partial stool samples of colonoscopynegative individuals were homogenized with stool homogenization buffer, spiked with different numbers of HCT116 colon cancer cells and kept at room temperature for 0, 24, 48, 72 and 144 h before DNA isolation. Analytical sensitivity was determined by the lowest number of cells that yielded positive test results by DNA methylation ormutation analysis. DNA methylation in FIT fluid was measured in 11 CRC patients and 20 control subjects. Results The analytical sensitivity for detecting DNA methylation was 3000 cells per gram stool, compared to 60000 cells per gram stool for detection of DNA mutations in the same stool samples. No degradation up to 72 h was noted when a conservation buffer was used. DNA methylation was detected in 4/11 CRC FIT samples and in none of the 20 control FIT samples. Conclusions Methylation based stool DNA testing showed a high analytical sensitivity for tumor DNA in partial stool samples, which was hardly influenced by DNA degradation over time, provided an adequate buffer was used. The feasibility of detecting DNA methylation in FIT fluid demonstrates the opportunity to combine testing for occult blood with DNA methylation in the same collection device. © International Society for Cellular Oncology 2012.
Oncomethylome science S.A. | Date: 2014-02-13
The present invention relates to methods and kits for identifying, diagnosing, prognosing, and monitoring cervical cancer. These methods include determining the methylation status or the expression levels of particular genes, or a combination thereof.
van Neste L.,Ghent University |
van Neste L.,OncoMethylome science SA |
Herman J.G.,The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Schuebel K.E.,The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
And 6 more authors.
Current Bioinformatics | Year: 2010
Epigenetics has become a cornerstone of cancer research and is an increasingly important factor in the continuous efforts to try and unravel the biology of oncogenesis. Consequently the analyses of epigenetic data have evolved towards genome wide and high-throughput approaches, generating large data sets for which computational data mining is indispensable. Bioinformatics has proven to be useful and beneficial for a plethora of tasks, going beyond elemental data management, and is now crucial for adequate candidate gene selection, data integration, comparison and correlation as well as providing insights into cancer biology. Computational approaches are used even in routine tasks like primer design, since multiple layers of information can be incorporated into a more efficient and consistent strategy. Almost every analysis feeds back information into both the biology and the tools we use during these experiments. As the cancer epigenetics field evolves rapidly, the combination with bioinformatics will create a synergy that increases our insights into cancer biology rapidly. This review summarizes some of the frequently used bioinformatics tools in large-scale or nextgeneration analyses in epigenetics that would not have been possible without the use of well-conceived computational strategies. © 2010 Bentham Science Publishers Ltd.
Ohm J.E.,Johns Hopkins University |
Ohm J.E.,University of North Dakota |
Mali P.,Johns Hopkins University |
Van Neste L.,Ghent University |
And 20 more authors.
Cancer Research | Year: 2010
The ability to induce pluripotent stem cells from committed, somatic human cells provides tremendous potential for regenerative medicine. However, there is a defined neoplastic potential inherent to such reprogramming that must be understood and may provide a model for understanding key events in tumorigenesis. Using genome-wide assays, we identify cancer-related epigenetic abnormalities that arise early during reprogramming and persist in induced pluripotent stem cell (iPS) clones. These include hundreds of abnormal gene silencing events, patterns of aberrant responses to epigenetic-modifying drugs resembling those for cancer cells, and presence in iPS and partially reprogrammed cells of cancer-specific gene promoter DNA methylation alterations. Our findings suggest that by studying the process of induced reprogramming, we may gain significant insight into the origins of epigenetic gene silencing associated with human tumorigenesis, and add to means of assessing iPS for safety. ©2010 AACR.