Advanced

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

Holm, Karolina LU ; Hegardt, Cecilia LU ; Staaf, Johan LU ; Vallon-Christersson, Johan LU ; Jönsson, Göran B LU ; Olsson, Håkan LU ; Borg, Åke LU and Ringnér, Markus LU (2010) In Breast Cancer Research 12(3).
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,... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research
volume
12
issue
3
publisher
BioMed Central
external identifiers
  • wos:000285689000012
  • scopus:77958540564
ISSN
1465-5411
DOI
10.1186/bcr2590
project
CREATE Health
language
English
LU publication?
yes
id
14295c79-84ab-42be-920b-40278c4f2726 (old id 1815013)
date added to LUP
2011-03-02 11:46:27
date last changed
2018-07-15 03:14:13
@article{14295c79-84ab-42be-920b-40278c4f2726,
  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.},
  articleno    = {R36},
  author       = {Holm, Karolina and Hegardt, Cecilia and Staaf, Johan and Vallon-Christersson, Johan and Jönsson, Göran B and Olsson, Håkan and Borg, Åke and Ringnér, Markus},
  issn         = {1465-5411},
  language     = {eng},
  number       = {3},
  publisher    = {BioMed Central},
  series       = {Breast Cancer Research},
  title        = {Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns},
  url          = {http://dx.doi.org/10.1186/bcr2590},
  volume       = {12},
  year         = {2010},
}