Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value
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 canc...
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Published in | Nature communications Vol. 6; no. 1; p. 5899 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
02.02.2015
Nature Publishing Group |
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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.
Triple-negative breast cancers (TNBCs) are a heterogeneous group of cancers with varying prognoses. Here, the authors carry out whole-genome methylation capture sequencing from TNBC samples and matched normal samples, and identify differentially methylated regions that define a potentially novel TNBC signature. |
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AbstractList | 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. 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. Triple-negative breast cancers (TNBCs) are a heterogeneous group of cancers with varying prognoses. Here, the authors carry out whole-genome methylation capture sequencing from TNBC samples and matched normal samples, and identify differentially methylated regions that define a potentially novel TNBC signature. |
ArticleNumber | 5899 |
Author | Trau, Matt Brown, Melissa A. Nair, Shalima S. Forbes, John F. Francis, Glenn D. Zotenko, Elena Qu, Wenjia Avery-Kiejda, Kelly A. Clark, Susan J. Stirzaker, Clare Peters, Kate M. Stone, Andrew Stein, Sandra Scott, Rodney J. Robinson, Mark D. Dobrovic, Alexander French, Juliet D. Song, Jenny Z. Locke, Warwick J. Korbie, Darren J. Armstong, Nicola J. |
Author_xml | – sequence: 1 givenname: Clare surname: Stirzaker fullname: Stirzaker, Clare organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research, St Vincent's Clinical School, University of NSW – sequence: 2 givenname: Elena surname: Zotenko fullname: Zotenko, Elena organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research, St Vincent's Clinical School, University of NSW – sequence: 3 givenname: Jenny Z. surname: Song fullname: Song, Jenny Z. organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research – sequence: 4 givenname: Wenjia surname: Qu fullname: Qu, Wenjia organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research – sequence: 5 givenname: Shalima S. surname: Nair fullname: Nair, Shalima S. organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research, St Vincent's Clinical School, University of NSW – sequence: 6 givenname: Warwick J. surname: Locke fullname: Locke, Warwick J. organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research, St Vincent's Clinical School, University of NSW – sequence: 7 givenname: Andrew surname: Stone fullname: Stone, Andrew organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research, St Vincent's Clinical School, University of NSW – sequence: 8 givenname: Nicola J. surname: Armstong fullname: Armstong, Nicola J. organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research, School of Mathematics and Statistics, University of Sydney – sequence: 9 givenname: Mark D. surname: Robinson fullname: Robinson, Mark D. organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research, Swiss Institute of Bioinformatics and Institute of Molecular Life Sciences, University of Zurich – sequence: 10 givenname: Alexander surname: Dobrovic fullname: Dobrovic, Alexander organization: Translational Genomics & Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute – sequence: 11 givenname: Kelly A. surname: Avery-Kiejda fullname: Avery-Kiejda, Kelly A. organization: School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle – sequence: 12 givenname: Kate M. surname: Peters fullname: Peters, Kate M. organization: School of Chemistry and Molecular Biosciences, University of Queensland – sequence: 13 givenname: Juliet D. surname: French fullname: French, Juliet D. organization: School of Chemistry and Molecular Biosciences, University of Queensland, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute – sequence: 14 givenname: Sandra surname: Stein fullname: Stein, Sandra organization: Pathology Queensland, Princess Alexandra Hospital – sequence: 15 givenname: Darren J. surname: Korbie fullname: Korbie, Darren J. organization: Australian Institute for Bioengineering and Nanotechnology, University of Queensland – sequence: 16 givenname: Matt surname: Trau fullname: Trau, Matt organization: School of Chemistry and Molecular Biosciences, University of Queensland, Australian Institute for Bioengineering and Nanotechnology, University of Queensland – sequence: 17 givenname: John F. surname: Forbes fullname: Forbes, John F. organization: School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle – sequence: 18 givenname: Rodney J. surname: Scott fullname: Scott, Rodney J. organization: School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Division of Molecular Medicine, Hunter Area Pathology Service and the Hunter Medical Research Institute, John Hunter Hospital – sequence: 19 givenname: Melissa A. surname: Brown fullname: Brown, Melissa A. organization: School of Chemistry and Molecular Biosciences, University of Queensland – sequence: 20 givenname: Glenn D. surname: Francis fullname: Francis, Glenn D. organization: Pathology Queensland, Princess Alexandra Hospital, Australian Institute for Bioengineering and Nanotechnology, University of Queensland – sequence: 21 givenname: Susan J. surname: Clark fullname: Clark, Susan J. email: s.clark@garvan.org.au organization: Cancer Division, Epigenetics Group, Garvan Institute of Medical Research, St Vincent's Clinical School, University of NSW |
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Snippet | Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumour stratification. Here, we perform whole-genome... |
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SubjectTerms | 13/106 631/208/514/1948 692/699/67/1347 692/699/67/68/2486 692/700/1750 Breast cancer Deoxyribonucleic acid DNA DNA Methylation - genetics DNA Methylation - physiology Epigenomics Female Humanities and Social Sciences Humans Methylation Molecular Sequence Data multidisciplinary Prognosis Science Science (multidisciplinary) Triple Negative Breast Neoplasms - genetics Triple Negative Breast Neoplasms - pathology |
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Title | Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value |
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