Epigenetic alterations to Polycomb targets precede malignant transition in a mouse model of breast cancer

Malignant breast cancer remains a major health threat to women of all ages worldwide and epigenetic variations on DNA methylation have been widely reported in cancers of different types. We profiled DNA methylation with ERRBS (Enhanced Reduced Representation Bisulfite Sequencing) across four main st...

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Bibliographic Details
Published in:Scientific reports 2018-04, Vol.8 (1), p.5535-12, Article 5535
Main Authors: Cai, Ying, Lin, Jhih-Rong, Zhang, Quanwei, O’Brien, Kelly, Montagna, Cristina, Zhang, Zhengdong D.
Format: Article
Language:English
Subjects:
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Adenoma
Biomarkers
Bisulfite
Breast cancer
Deoxyribonucleic acid
DNA
DNA methylation
DNA sequencing
Epigenetics
Glands
Health risks
Humanities and Social Sciences
Hyperplasia
multidisciplinary
Polycomb group proteins
Science
Science (multidisciplinary)
Tumors
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Summary:Malignant breast cancer remains a major health threat to women of all ages worldwide and epigenetic variations on DNA methylation have been widely reported in cancers of different types. We profiled DNA methylation with ERRBS (Enhanced Reduced Representation Bisulfite Sequencing) across four main stages of tumor progression in the MMTV-PyMT mouse model (hyperplasia, adenoma/mammary intraepithelial neoplasia, early carcinoma and late carcinoma), during which malignant transition occurs. We identified a large number of differentially methylated cytosines (DMCs) in tumors relative to age-matched normal mammary glands from FVB mice. Despite similarities, the methylation differences of the premalignant stages were distinct from the malignant ones. Many differentially methylated loci were preserved from the first to the last stage throughout tumor progression. Genes affected by methylation gains were enriched in Polycomb repressive complex 2 (PRC2) targets, which may present biomarkers for early diagnosis and targets for treatment.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-24005-x