Hierarchical clustering of breast cancer methylomes revealed differentially methylated and expressed breast cancer genes

I. Hsuan Lin, Dow Tien Chen, Yi Feng Chang, Yu Ling Lee, Chia Hsin Su, Ching Cheng, Yi Chien Tsai, Swee Chuan Ng, Hsiao Tan Chen, Mei Chen Lee, Hong Wei Chen, Shih Hui Suen, Yu Cheng Chen, Tze Tze Liu, Chuan Hsiung Chang, Ming Ta Hsu

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23 引文 斯高帕斯(Scopus)

摘要

Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs) and the hypomethylation of the megabase-sized partially methylated domains (PMDs) are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI) was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma) dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation.
原文英語
文章編號e0118453
期刊PLoS One
10
發行號2
DOIs
出版狀態已發佈 - 二月 23 2015
對外發佈

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 農業與生物科學 (全部)

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