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Breast Cancer Res. 2010;12(3):R36. doi: 10.1186/bcr2590. Epub 2010 Jun 18.

Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns.

Author information

1
Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, Lund, Sweden. karolina.holm@med.lu.se

Abstract

INTRODUCTION:

Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles.

METHODS:

We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay.

RESULTS:

Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation.

CONCLUSIONS:

We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers.

PMID:
20565864
PMCID:
PMC2917031
DOI:
10.1186/bcr2590
[Indexed for MEDLINE]
Free PMC Article

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