A DNA methylation-based definition of biologically distinct breast cancer subtypes.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsStefansson, Olafur A
Jonasson, Jon G
MetadataShow full item record
CitationMol Oncol 2015, 9 (3):555-68
AbstractIn cancer, epigenetic states are deregulated and thought to be of significance in cancer development and progression. We explored DNA methylation-based signatures in association with breast cancer subtypes to assess their impact on clinical presentation and patient prognosis. DNA methylation was analyzed using Infinium 450K arrays in 40 tumors and 17 normal breast samples, together with DNA copy number changes and subtype-specific markers by tissue microarrays. The identified methylation signatures were validated against a cohort of 212 tumors annotated for breast cancer subtypes by the PAM50 method (The Cancer Genome Atlas). Selected markers were pyrosequenced in an independent validation cohort of 310 tumors and analyzed with respect to survival, clinical stage and grade. The results demonstrate that DNA methylation patterns linked to the luminal-B subtype are characterized by CpG island promoter methylation events. In contrast, a large fraction of basal-like tumors are characterized by hypomethylation events occurring within the gene body. Based on these hallmark signatures, we defined two DNA methylation-based subtypes, Epi-LumB and Epi-Basal, and show that they are associated with unfavorable clinical parameters and reduced survival. Our data show that distinct mechanisms leading to changes in CpG methylation states are operative in different breast cancer subtypes. Importantly, we show that a few selected proxy markers can be used to detect the distinct DNA methylation-based subtypes thereby providing valuable information on disease prognosis.
DescriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.
- An integrated genomics analysis of epigenetic subtypes in human breast tumors links DNA methylation patterns to chromatin states in normal mammary cells.
- Authors: Holm K, Staaf J, Lauss M, Aine M, Lindgren D, Bendahl PO, Vallon-Christersson J, Barkardottir RB, Höglund M, Borg Å, Jönsson G, Ringnér M
- Issue date: 2016 Feb 29
- Distinct patterns of promoter CpG island methylation of breast cancer subtypes are associated with stem cell phenotypes.
- Authors: Park SY, Kwon HJ, Choi Y, Lee HE, Kim SW, Kim JH, Kim IA, Jung N, Cho NY, Kang GH
- Issue date: 2012 Feb
- Molecular Subtype-Specific Expression of MicroRNA-29c in Breast Cancer Is Associated with CpG Dinucleotide Methylation of the Promoter.
- Authors: Poli E, Zhang J, Nwachukwu C, Zheng Y, Adedokun B, Olopade OI, Han YJ
- Issue date: 2015
- Epigenetic and genetic burden measures are associated with tumor characteristics in invasive breast carcinoma.
- Authors: O'Sullivan DE, Johnson KC, Skinner L, Koestler DC, Christensen BC
- Issue date: 2016 May 3
- Expression and methylation patterns partition luminal-A breast tumors into distinct prognostic subgroups.
- Authors: Netanely D, Avraham A, Ben-Baruch A, Evron E, Shamir R
- Issue date: 2016 Jul 7