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:
https://lup.lub.lu.se/record/1815013
- author
- 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
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Breast Cancer Research
- volume
- 12
- issue
- 3
- article number
- R36
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000285689000012
- scopus:77958540564
- pmid:20565864
- ISSN
- 1465-5411
- DOI
- 10.1186/bcr2590
- language
- English
- LU publication?
- yes
- id
- 14295c79-84ab-42be-920b-40278c4f2726 (old id 1815013)
- date added to LUP
- 2016-04-01 10:35:13
- date last changed
- 2022-05-16 07:51:19
@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.}},
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 (BMC)}},
series = {{Breast Cancer Research}},
title = {{Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns}},
url = {{https://lup.lub.lu.se/search/files/1969349/1852052.pdf}},
doi = {{10.1186/bcr2590}},
volume = {{12}},
year = {{2010}},
}