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

Författare:
  • Karolina Holm
  • Cecilia Hegardt
  • Johan Staaf
  • Johan Vallon-Christersson
  • Göran B Jönsson
  • Håkan Olsson
  • Åke Borg
  • Markus Ringnér
Publiceringsår: 2010
Språk: Engelska
Publikation/Tidskrift/Serie: Breast Cancer Research
Volym: 12
Nummer: 3
Dokumenttyp: Artikel i tidskrift
Förlag: BioMed Central

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • CREATE Health
  • ISSN: 1465-5411
Markus Ringnér
E-post: markus [dot] ringner [at] biol [dot] lu [dot] se

Forskningsingenjör

Molekylär cellbiologi

B-A317

Sölvegatan 35, Lund

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