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Series GSE75067 Query DataSets for GSE75067
Status Public on Feb 29, 2016
Title Genome-wide DNA methylation analysis of breast cancer
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Aberrant DNA methylation is frequently observed in breast cancer. However, the relationship between methylation patterns and the heterogeneity of breast cancer has not been comprehensively characterized. Whole-genome DNA methylation analysis using 450K Illumina BeadArrays was performed on 188 human breast tumors. Unsupervised bootstrap consensus clustering was performed to identify DNA methylation epigenetic subgroups (epitypes). The Cancer Genome Atlas data, incluing methylation profiles of 669 human breast tumors, was utilized for validation. The identified epitypes were characterized by integration with publicly available genome-wide data, including gene expression levels, DNA copy numbers, whole-exome sequencing data, and chromatin states. We identified seven breast cancer epitypes. One epitype was distinctly associated with basal-like tumors and with BRCA1 mutations, one epitype contained a subset of ERBB2-amplified tumors characterized by multiple additional amplifications and the most complex genomes, and one epitype displayed a methylation profile similar to normal epithelial cells. Luminal tumors were stratified into the remaining four epitypes, with differences in promoter hypermethylation, global hypomethylation, proliferative rates and genomic instability. We observed two dominant patterns of aberrant methylation in breast cancer. One pattern, constitutively methylated in both basal-like and luminal breast cancer, was linked to genes with promoters in a Polycomb-repressed state in normal epithelial cells and displayed no correlation to gene expression levels. The second pattern correlated with gene expression levels and was associated with methylation in luminal tumors and genes with active promoters in normal epithelial cells. Our results suggest that hypermethylation patterns in basal-like breast cancer may have limited influence on tumor progression and instead reflects the repressed chromatin state of the tissue of origin. On the contrary, hypermethylation patterns specific to luminal breast cancer influence gene expression, may contribute to tumor progression, and may present an actionable epigenetic alteration in some luminal breast cancers.
Overall design Genome-wide DNA methylation analysis of 188 breast cancers using Illumina Human Methylation 450K Beadchips.
Contributor(s) Ringnér M, Holm K, Staaf J, Jönsson G
Citation(s) 26923702
Submission date Nov 16, 2015
Last update date Mar 22, 2019
Contact name Markus Ringner
Organization name Lund University
Street address Sölvegatan 37
City Lund
ZIP/Postal code 22381
Country Sweden
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (188)
GSM1941862 TAX577409
GSM1941863 TAX577773
GSM1941864 TAX577414
BioProject PRJNA302431

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Supplementary file Size Download File type/resource
GSE75067_RAW.tar 183.1 Mb (http)(custom) TAR
GSE75067_methylation_raw.txt.gz 446.6 Mb (ftp)(http) TXT
GSE75067_sample_annotations.txt.gz 27.4 Kb (ftp)(http) TXT
Raw data is available on Series record
Processed data included within Sample table

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