Project description:As a non-invasive blood testing, the detection of cell-free DNA (cfDNA) methylation in plasma is raising increasing interest due to its diagnostic and biology applications. Although extensively used in cfDNA methylation analysis, bisulfite sequencing is less cost-effective. Through enriching methylated cfDNA fragments with MeDIP followed by deep sequencing, we aimed to characterize cfDNA methylome in cancer patients. In this study, we investigated the cfDNA methylation patterns in lung cancer patients by MeDIP-seq. MEDIPS package was used for the identification of differentially methylated regions (DMRs) between patients and normal ones. Overall, we identified 330 differentially methylated regions (DMRs) in gene promoter regions, 33 hypermethylation and 297 hypomethylation respectively, by comparing lung cancer patients and healthy individuals as controls. The 33 hypermethylation regions represent 32 genes. Some of the genes had been previously reported to be associated with lung cancers, such as GAS7, AQP10, HLF, CHRNA9 and HOPX. Taken together, our study provided an alternative method of cfDNA methylation analysis in lung cancer patients with potential clinical applications.
Project description:To research the relationship between methylation of genomic DNA and lung cancer, lung cancer and correlated normal tissue were used to extract genomic DNA, followed with detection of methylation.
Project description:Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive differences in therapy response and outcomes. Histologic transformation to castration-resistant neuroendocrine prostate cancer (CRPC-NE) is associated with distinct epigenetic alterations, including acquired changes in DNA methylation. The current diagnosis of CRPC-NE is challenging and relies on metastatic biopsy. Here, we developed a targeted DNA methylation assay based on the analysis of large tissue datasets to detect CRPC-NE using plasma cell-free DNA (cfDNA) non-invasively. The assay quantifies tumor content and a phenotype evidence score that captures the spectrum of CRPC phenotypes, leveraging a few hundred informative genomic regions to also inform the expression and/or transcriptional state of genes of interest. We qualified the assay in independent clinical cohorts, including 158 plasma samples, achieving a phenotypic evidence score AUC > 0.93 for detecting pathology-confirmed CRPC-NE, and revealing associations between methylation-defined tumor content and clinical outcomes in two prospective phase 2 clinical trials (NCT01799278 and NCT00514540) designed toward aggressive variant CRPC and CRPC-NE, supporting the application of targeted DNA methylation for CRPC-NE detection and patient stratification.
Project description:We used a highly sensitive nano-5hmC-Seal method and profiled the genome-wide distribution of 5-hydroxymethylcytosine (5hmC) in plasma cell-free DNA (cfDNA) from 384 patients with bladder, breast, colorectal, kidney, lung, or prostate cancer and 221 controls. We used machine learning and developed plasma cfDNA 5hmC signatures that are highly sensitive for cancer detection and cancer origin determination. We also identified genes and signaling pathways with aberrant DNA hydroxymethylation in six cancers.