Journal article
Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value
Nature Communications, Vol.6
2015
Abstract
Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumour stratification. Here, we perform whole-genome methylation capture sequencing on small amounts of DNA isolated from formalin-fixed, paraffin-embedded tissue from triple-negative breast cancer (TNBC) and matched normal samples. We identify differentially methylated regions (DMRs) enriched with promoters associated with transcription factor binding sites and DNA hypersensitive sites. Importantly, we stratify TNBCs into three distinct methylation clusters associated with better or worse prognosis and identify 17 DMRs that show a strong association with overall survival, including DMRs located in the Wilms tumour 1 (WT1) gene, bi-directional-promoter and antisense WT1-AS. Our data reveal that coordinated hypermethylation can occur in oestrogen receptor-negative disease, and that characterizing the epigenetic framework provides a potential signature to stratify TNBCs. Together, our findings demonstrate the feasibility of profiling the cancer methylome with limited archival tissue to identify regulatory regions associated with cancer.
Details
- Title
- Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value
- Authors/Creators
- C. Stirzaker (Author/Creator) - Garvan Institute of Medical ResearchE. Zotenko (Author/Creator) - Garvan Institute of Medical ResearchJ.Z. Song (Author/Creator) - Garvan Institute of Medical ResearchW. Qu (Author/Creator) - Garvan Institute of Medical ResearchS.S. Nair (Author/Creator) - Garvan Institute of Medical ResearchW.J. Locke (Author/Creator) - Garvan Institute of Medical ResearchA. Stone (Author/Creator) - Garvan Institute of Medical ResearchN.J. Armstong (Author/Creator) - Garvan Institute of Medical ResearchM.D. Robinson (Author/Creator) - Garvan Institute of Medical ResearchA. Dobrovic (Author/Creator) - Epigenomics (Germany)K.A. Avery-Kiejda (Author/Creator) - University of Newcastle AustraliaK.M. Peters (Author/Creator) - The University of QueenslandJ.D. French (Author/Creator) - QIMR Berghofer Medical Research InstituteS. Stein (Author/Creator) - Princess Alexandra HospitalD.J. Korbie (Author/Creator) - The University of QueenslandM. Trau (Author/Creator) - The University of QueenslandJ.F. Forbes (Author/Creator) - University of Newcastle AustraliaR.J. Scott (Author/Creator) - John Hunter HospitalM.A. Brown (Author/Creator) - The University of QueenslandG.D. Francis (Author/Creator) - Princess Alexandra HospitalS.J. Clark (Author/Creator) - Garvan Institute of Medical Research
- Publication Details
- Nature Communications, Vol.6
- Publisher
- Nature Publishing Group
- Identifiers
- 991005542616607891
- Copyright
- © 2015 Macmillan Publishers Limited.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.54 Molecular & Cell Biology - Genetics
- 1.54.100 Epigenetic Regulation
- Web Of Science research areas
- Oncology
- ESI research areas
- Clinical Medicine