Showing papers by "María Berdasco published in 2011"
TL;DR: This phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles that may be useful for early detection and cancer prevention studies.
Abstract: Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance, we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and quantitative methylation specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage design consisting of discovery and prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (κ = 0.64), HOXA9 (κ = 0.60), NID2 (κ = 0.60), and EDNRB (κ = 0.60) had a moderate to substantial agreement with clinical diagnosis in the discovery screen. HOXA9 had 68% sensitivity, 100% specificity, and a 0.81 Area Under the Curve (AUC). NID2 had 71% sensitivity, 100% specificity, and a 0.79 AUC. In the prevalence screen, HOXA9 (κ = 0.82) and NID2 (κ = 0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity, and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity, and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity, and a 0.97 AUC. In saliva, from OSCC cases and controls, HOXA9 had 75% sensitivity, 53% specificity, and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity, and a 0.73 AUC. This phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.
115 citations
TL;DR: It is clear from the evidence that DNA methylation is necessary for controlling stem cell proliferation and differentiation, but their exact contribution in each lineage program is still unclear.
Abstract: Owing to their potential for differentiation into multiple cell types, multipotent stem cells extracted from many adult tissues are an attractive stem cell resource for the replacement of damaged tissues in regenerative medicine. The requirements for cellular differentiation of an adult stem cell are a loss of proliferation potential and a gain of cell-type identity. These processes could be restricted by epigenetic modifications that prevent the risks of lineage-unrelated gene expression or the undifferentiated features of stem cells in adult somatic cells. In this review, we focus on the role of DNA methylation in controlling the transcriptional activity of genes important for self-renewal, the dynamism of CpG methylation of tissue-specific genes during several differentiation programs, and whether the multilineage potential of adult stem cells could be imposed early in the original precursor stem cells through CpG methylation. Additionally, we draw attention to the role of DNA methylation in adult stem cell differentiation by reviewing the reports on spontaneous differentiation after treatment with demethylating agents and by considering the evidence provided by reprogramming of somatic cells into undifferentiated cells (that is, somatic nuclear transfer or generation of induced pluripotent cells). It is clear from the evidence that DNA methylation is necessary for controlling stem cell proliferation and differentiation, but their exact contribution in each lineage program is still unclear. As a consequence, in a clinical setting, caution should be exerted before employing adult stem cells or their derivatives in regenerative medicine and appropriate tests should be applied to ensure the integrity of the genome and epigenome.
95 citations