Integrated analyses of DNA methylation and hydroxymethylation reveal tumor suppressive roles of ECM1, ATF5, and EOMES in human hepatocellular carcinoma.

Abstract:

BACKGROUND:Differences in 5-hydroxymethylcytosine, 5hmC, distributions may complicate previous observations of abnormal cytosine methylation statuses that are used for the identification of new tumor suppressor gene candidates that are relevant to human hepatocarcinogenesis. The simultaneous detection of 5-methylcytosine and 5-hydroxymethylcytosine is likely to stimulate the discovery of aberrantly methylated genes with increased accuracy in human hepatocellular carcinoma. RESULTS:Here, we performed ultra-performance liquid chromatography/tandem mass spectrometry and single-base high-throughput sequencing, Hydroxymethylation and Methylation Sensitive Tag sequencing, HMST-seq, to synchronously measure these two modifications in human hepatocellular carcinoma samples. After identification of differentially methylated and hydroxymethylated genes in human hepatocellular carcinoma, we integrate DNA copy-number alterations, as determined using array-based comparative genomic hybridization data, with gene expression to identify genes that are potentially silenced by promoter hypermethylation. CONCLUSIONS:We report a high enrichment of genes with epigenetic aberrations in cancer signaling pathways. Six genes were selected as tumor suppressor gene candidates, among which, ECM1, ATF5 and EOMES are confirmed via siRNA experiments to have potential anti-cancer functions.

journal_name

Genome Biol

journal_title

Genome biology

authors

Gao F,Xia Y,Wang J,Lin Z,Ou Y,Liu X,Liu W,Zhou B,Luo H,Zhou B,Wen B,Zhang X,Huang J

doi

10.1186/s13059-014-0533-9

subject

Has Abstract

pub_date

2014-12-03 00:00:00

pages

533

issue

12

eissn

1474-7596

issn

1474-760X

pii

s13059-014-0533-9

journal_volume

15

pub_type

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