Source:http://linkedlifedata.com/resource/pubmed/id/21641572
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2011-6-27
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| pubmed:abstractText |
We broadly profiled DNA methylation in breast cancers (n = 351) and benign parenchyma (n = 47) for correspondence with disease phenotype, using FFPE diagnostic surgical pathology specimens. Exploratory analysis revealed a distinctive primary invasive carcinoma subclass featuring extreme global methylation deviation. Subsequently, we tested the correlation between methylation remodeling pervasiveness and malignant biological features. A methyl deviation index (MDI) was calculated for each lesion relative to terminal ductal-lobular unit baseline, and group comparisons revealed that high-grade and short-survival estrogen receptor-positive (ER(+)) cancers manifest a significantly higher MDI than low-grade and long-survival ER(+) cancers. In contrast, ER(-) cancers display a significantly lower MDI, revealing a striking epigenomic distinction between cancer hormone receptor subtypes. Kaplan-Meier survival curves of MDI-based risk classes showed significant divergence between low- and high-risk groups. MDI showed superior prognostic performance to crude methylation levels, and MDI retained prognostic significance (P < 0.01) in Cox multivariate analysis, including clinical stage and pathological grade. Most MDI targets individually are significant markers of ER(+) cancer survival. Lymphoid and mesenchymal indexes were not substantially different between ER(+) and ER(-) groups and do not explain MDI dichotomy. However, the mesenchymal index was associated with ER(+) cancer survival, and a high lymphoid index was associated with medullary carcinoma. Finally, a comparison between metastases and primary tumors suggests methylation patterns are established early and maintained through disease progression for both ER(+) and ER(-) tumors.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
|
| pubmed:issn |
1525-2191
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| pubmed:author |
pubmed-author:BibikovaMarinaM,
pubmed-author:BilkeSvenS,
pubmed-author:DavisSeanS,
pubmed-author:FanJian-BingJB,
pubmed-author:JaegerErichE,
pubmed-author:KillianJ KeithJK,
pubmed-author:KillianM ScottMS,
pubmed-author:MeltzerPaul SPS,
pubmed-author:SmithWilliam IWIJr,
pubmed-author:WalkerRobert LRL,
pubmed-author:WaterfallJoshua JJJ
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| pubmed:copyrightInfo |
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
|
| pubmed:issnType |
Electronic
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| pubmed:volume |
179
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
55-65
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| pubmed:meshHeading |
pubmed-meshheading:21641572-Aged,
pubmed-meshheading:21641572-Breast,
pubmed-meshheading:21641572-Breast Neoplasms,
pubmed-meshheading:21641572-Carcinoma, Ductal, Breast,
pubmed-meshheading:21641572-Carcinoma, Lobular,
pubmed-meshheading:21641572-Carcinoma, Medullary,
pubmed-meshheading:21641572-DNA Methylation,
pubmed-meshheading:21641572-Epigenomics,
pubmed-meshheading:21641572-Female,
pubmed-meshheading:21641572-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21641572-Humans,
pubmed-meshheading:21641572-Immunophenotyping,
pubmed-meshheading:21641572-Longitudinal Studies,
pubmed-meshheading:21641572-Lymphocytes,
pubmed-meshheading:21641572-Mesoderm,
pubmed-meshheading:21641572-Middle Aged,
pubmed-meshheading:21641572-Neoplasm Invasiveness,
pubmed-meshheading:21641572-Prognosis,
pubmed-meshheading:21641572-Receptors, Estrogen,
pubmed-meshheading:21641572-Survival Rate,
pubmed-meshheading:21641572-Tumor Markers, Biological
|
| pubmed:year |
2011
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| pubmed:articleTitle |
A methyl-deviator epigenotype of estrogen receptor-positive breast carcinoma is associated with malignant biology.
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| pubmed:affiliation |
Genetics Branch, National Cancer Institute, Bethesda, MD 20892, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study
|