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Subtype-specific CpG island shore methylation and mutation patterns in 30 breast cancer cell lines

Cited 7 time in Web of Science Cited 7 time in Scopus
Authors
Chae, Heejoon; Lee, Sangseon; Nephew, Kenneth P; Kim, Sun
Issue Date
2016-12-23
Publisher
BioMed Central
Citation
BMC Systems Biology, 10(Suppl 4):116
Keywords
Breast cancerSubtypeDNA methylationCpGI shoreMutation
Description
This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
Abstract
Abstract

Background
Aberrant epigenetic modifications, including DNA methylation, are key regulators of gene activity in tumorigenesis. Breast cancer is a heterogeneous disease, and large-scale analyses indicate that tumor from normal and benign tissues, as well as molecular subtypes of breast cancer, can be distinguished based on their distinct genomic, transcriptomic, and epigenomic profiles. In this study, we used affinity-based methylation sequencing data in 30 breast cancer cell lines representing functionally distinct cancer subtypes to investigate methylation and mutation patterns at the whole genome level.


Results
Our analysis revealed significant differences in CpG island (CpGI) shore methylation and mutation patterns among breast cancer subtypes. In particular, the basal-like B type, a highly aggressive form of the disease, displayed distinct CpGI shore hypomethylation patterns that were significantly associated with downstream gene regulation. We determined that mutation rates at CpG sites were highly correlated with DNA methylation status and observed distinct mutation rates among the breast cancer subtypes. These findings were validated by using targeted bisulfite sequencing of differentially expressed genes (n=85) among the cell lines.


Conclusions
Our results suggest that alterations in DNA methylation play critical roles in gene regulatory process as well as cytosine substitution rates at CpG sites in molecular subtypes of breast cancer.
Language
English
URI
https://hdl.handle.net/10371/100396
DOI
https://doi.org/10.1186/s12918-016-0356-2
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College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Computer Science and Engineering (컴퓨터공학부)Journal Papers (저널논문_컴퓨터공학부)
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