Unknown,Transcriptomics,Genomics,Proteomics

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Analysis of Promoter Methylation in Breast Cancer


ABSTRACT: Promoter methylation was assayed in a number of breast cancer and control normal samples along with the effects of 5'-aza-2'-deoxycytidine on breast cancer cell line transcriptomes. Aberrant promoter hypermethylation is frequently observed in cancer. The potential for this to contribute to tumour development depends on whether the genes affected are repressed because of their methylation. Many aberrantly methylated genes play important roles in development and are bivalently marked in ES cells suggesting that their aberrant methylation may reflect developmental processes. We investigated this possibility by analysing promoter methylation in 19 breast cancer cell lines, 10 normal tissues and 47 primary breast tumours. In order to determine the role of DNA methylation in silencing genes in breast cancer, we also examined the effects of the demethylating agent 5-aza-2?-deoxycytidine on gene expression in 3 breast cancer cell lines and HCT116 cells. Gene expression changes were also assayed in the DNA methyltransferase deficient HCT116 DKO cell line. Our findings implicate aberrant DNA methylation as a marker of cell lineage rather than tumour progression and suggest that, in most cases, it does not cause the repression with which it is associated. A number of human breast cancer cell lines, breast tumours and normal tissues were analysed on Illumina Infinium Methylation27 Beadchips to assay promoter methylation. Selected cell lines were analysed on expression arrays before and after treatment with 5-aza-2'-deoxycytidine.

ORGANISM(S): Homo sapiens

SUBMITTER: Duncan Sproul 

PROVIDER: E-GEOD-26990 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptionally repressed genes become aberrantly methylated and distinguish tumors of different lineages in breast cancer.

Sproul Duncan D   Nestor Colm C   Culley Jayne J   Dickson Jacqueline H JH   Dixon J Michael JM   Harrison David J DJ   Meehan Richard R RR   Sims Andrew H AH   Ramsahoye Bernard H BH  

Proceedings of the National Academy of Sciences of the United States of America 20110228 11


Aberrant promoter hypermethylation is frequently observed in cancer. The potential for this mechanism to contribute to tumor development depends on whether the genes affected are repressed because of their methylation. Many aberrantly methylated genes play important roles in development and are bivalently marked in ES cells, suggesting that their aberrant methylation may reflect developmental processes. We investigated this possibility by analyzing promoter methylation in 19 breast cancer cell l  ...[more]

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