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Series GSE63421 Query DataSets for GSE63421
Status Public on Feb 03, 2015
Title 5-hydroxymethylcytosine marks promoters in colon that resist hypermethylation in cancer [Methylation450 Array]
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary The discovery of cytosine hydroxymethylation (5-hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behavior in colon cancer. 5-hmC is globally reduced in proliferating cells such as colon tumors and the gut crypt progenitors, from which tumors can arise. Here, we show that colorectal tumors and cancer cells express Ten-Eleven Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5-hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5-hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells. Together our results indicate that promoters that acquire 5-hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5-hmC in tumors. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.
Overall design Six samples were analyzed. 2 biological replicates each of HCT116 cells stably transfected with an empty vector control (TET_KD_Plk), with shRNA to TET2 (TET_KD_2C) and with shRNA to TET2 and TET3 (TET_KD_2.3)
Contributor(s) Uribe-Lewis S, Halim S, Defrance M
Citation(s) 25853800
Submission date Nov 18, 2014
Last update date Mar 22, 2019
Contact name Chandra Chilamakuri
Organization name Cancer Research UK Cambridge Institute
Street address Robinson Way
City Cambridge
ZIP/Postal code CB2 0RE
Country United Kingdom
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (6)
GSM1548467 HCT116_shRNA_emptyvector_1
GSM1548468 HCT116_shRNA_emptyvector_2
GSM1548469 HCT116_shRNA_TET2_1
This SubSeries is part of SuperSeries:
GSE47592 5-hydroxymethylcytosine marks promoters in colon that resist hypermethylation in cancer
BioProject PRJNA267708

Download family Format
SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE63421_RAW.tar 183.1 Mb (http)(custom) TAR
GSE63421_signals.txt.gz 12.8 Mb (ftp)(http) TXT
Processed data included within Sample table

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