Genomics

Dataset Information

297

Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma


ABSTRACT: DNA methylation at the 5-position of cytosine (5-mC) is a key epigenetic mark critical for varius biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the Ten-Eleven Translocation (TET) family of DNA hydroxylases. Here we report that "loss of 5-hmC" is an epigenetic hallmark of melanoma with diagonostic and prognostic implications. Genome-wide mapping of 5-hmC in nevi and melanomas for the first time revealed loss of 5-hmC landscape in the melanoma epigenome. Downregulation of Isocitrate Dehydrogenase 2 (IDH2) and TET family enzymes proved to be one of the mechanisms underlying the loss of 5-hmC during melanoma development, and rebuilding the 5-hmC landscape in the melanoma epigenome by reintroducing active TET2 or IDH2 suppressed melanoma growth and increased tumor-free survival. Thus, our study establishes that "loss of 5-hmC" is a new epigenetic hallmark of melanoma and links IDH and TET family enzymes-mediated 5-hmC putative tumor suppressor pathway to the suppression of melanoma progression. Determine the genome-wide distribution of 5mC and 5hmC in benign nevus tissue, melanoma tissue, A2058 MOCK cells (overexpressing empty vector), A2058 TET2 cells (overexpressing wild type human TET), and A2058 TET2M cells (overexpressing mutant human TET).

ORGANISM(S): Homo sapiens  

SUBMITTER: Yufei Xu   Yujiang Shi  Feizhen Wu 

PROVIDER: E-GEOD-38231 | ArrayExpress | 2012-09-18

SECONDARY ACCESSION(S): SRP013379GSE38231PRJNA167460

REPOSITORIES: GEO, ArrayExpress, ENA

altmetric image

Publications


DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Here, we report that "loss of 5-hmC" is an epigenetic hallmark of melanoma, with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of the 5-hmC landscape in the melanoma epigenome. We show that downr  ...[more]

Similar Datasets

2015-02-03 | E-GEOD-47590 | ArrayExpress
2015-02-03 | E-GEOD-63421 | ArrayExpress
2012-08-09 | E-GEOD-31351 | ArrayExpress
| GSE52882 | GEO
2018-10-10 | GSE121095 | GEO
2016-07-25 | E-GEOD-72481 | ArrayExpress
2014-05-01 | E-MEXP-3911 | ArrayExpress
2015-07-30 | E-GEOD-69403 | ArrayExpress
2012-08-09 | E-GEOD-31352 | ArrayExpress
2015-02-20 | E-GEOD-66114 | ArrayExpress