The dynamics and prognostic potential of DNA methylation changes at stem cell gene loci in women's cancer.

PLoS Genetics
Joanna ZhuangMartin Widschwendter

Abstract

Aberrant DNA methylation is an important cancer hallmark, yet the dynamics of DNA methylation changes in human carcinogenesis remain largely unexplored. Moreover, the role of DNA methylation for prediction of clinical outcome is still uncertain and confined to specific cancers. Here we perform the most comprehensive study of DNA methylation changes throughout human carcinogenesis, analysing 27,578 CpGs in each of 1,475 samples, ranging from normal cells in advance of non-invasive neoplastic transformation to non-invasive and invasive cancers and metastatic tissue. We demonstrate that hypermethylation at stem cell PolyComb Group Target genes (PCGTs) occurs in cytologically normal cells three years in advance of the first morphological neoplastic changes, while hypomethylation occurs preferentially at CpGs which are heavily Methylated in Embryonic Stem Cells (MESCs) and increases significantly with cancer invasion in both the epithelial and stromal tumour compartments. In contrast to PCGT hypermethylation, MESC hypomethylation progresses significantly from primary to metastatic cancer and defines a poor prognostic signature in four different gynaecological cancers. Finally, we associate expression of TET enzymes, which are involv...Continue Reading

Associated Datasets

Feb 20, 2012
Feb 23, 2012·Andrew TeschendorffMartin Widschwendter
Feb 20, 2012·Andrew E Teschendorff
Jul 18, 2011

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Citations

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Methods Mentioned

BETA
methylation
chip
PCR

Software Mentioned

MapInfo
Gene Set Enrichment Analysis ( GSEA )
GSEA
Bioconductor
Illumina
Beadstudio

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