Dataset Information

Epigenome signatures during gastric carcinogenesis based on next generation sequencing analysis [MBD-Seq]

ABSTRACT: Because gastric cancer cells already had genetic and epigenetic alterations which can affect the gastric carcinogenesis, we tried to characterize genetic and epigenetic changes during gastric carcinogenesis. To do this, we performed MBD sequencing and RRBS sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE55157 | GEO | 2015/09/01

SECONDARY ACCESSION(S): PRJNA238874

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Dysregulation of the epigenome is a common event in malignancy. However, deciphering the earliest cancer associated epigenetic events remains a challenge. Cancer epigenome studies to date have primarily utilised cancer cell lines or clinical samples, where it is difficult to identify the initial epigenetic lesions from those that occur over time. Here, we analysed the epigenome of normal Human Mammary Epithelial Cells (HMEC) and a matched variant cell population (vHMEC) that has escaped senescence and undergone partial carcinogenic transformation. Using this model system we sought to identify the earliest epigenetic changes that potentially occur during carcinogenesis. First we show that the transcriptome of vHMEC resembles that of basal-like breast cancer. Moreover, in vHMEC there is significant deregulation of MYC, p53, EZH2/polycomb, the Aryl Hydrocarbon Receptor (AHR) and miRNAs-143, 145, 199a and 519a at the transcriptional level. Second, we find that vHMEC exhibit genome-wide changes in DNA methylation affecting key cancer-associated pathways. Hypermethylation predominately impacted gene promoters (particularly those targeted by AHR and TP53) and polycomb associated loci, whereas hypomethylation frequently affected enhancers. Next we show that long range epigenetic deregulation occurred in vHMEC involving concordant change in chromatin modification and gene expression across ~0.5-1Mb regions. Finally, we demonstrate that the DNA methylation changes we observe in vHMECs, occur in basal-like breast cancer (notably FOXA1 hypermethylation).. Overall our results suggest that the first steps of carcinogenesis are associated with a co-ordinated deregulation of DNA methylation and chromatin modification spanning a range of genomic loci potentially targeted by key transcription factors and a corresponding deregulation of transcriptional networks. We sought to study the chromatin modification profile of human mammary epithelial cells (HMEC) and a matched isogenic variant population (vHMEC) utilising ChIP-seq. ChIP was performed against H3K27ac, H3K36me3 and H3K27me3 for a HMEC and vHMEC timpoint in one donor. H3K4me3 CHIP was performed in two donors, which were treated as biological replicates.

Dataset Information

Epigenome signatures during gastric carcinogenesis based on next generation sequencing analysis [MBD-Seq]

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure