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Epigenomics. 2015 Oct;7(7):1099-110. doi: 10.2217/epi.15.43. Epub 2015 May 18.

Chromosome X genomic and epigenomic aberrations and clinical implications in breast cancer by base resolution profiling.

Author information

1
Department of Health Sciences Research, Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN 55905, USA.
2
Medical School, University of Minnesota, Minneapolis, MN 55455, USA.
3
Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA.

Abstract

AIM:

Abnormal inactivation or loss of inactivated X chromosome (Xi) is implicated in women's cancer. However, the underlying mechanisms and clinical relevance are little known.

MATERIALS & METHODS:

High-throughput sequencing was conducted on breast cancer cell lines for copy number, RNA expression and 5'-methylcytosine in ChrX. The results were examined in primary breast tumors.

RESULTS & CONCLUSION:

Breast cancer cells demonstrated reduced or total loss of hemimethylation. Most cell lines lost part or one of X chromosomes. Cell lines without ChrX loss were more active in gene expression. DNA methylation was corroborated with Xi control lincRNA XIST. Similar transcriptome and DNA methylation changes were observed in primary breast cancer datasets with clinical phenotype associations. Dramatic genomic and epigenomic changes in ChrX may be used for potential diagnostic or prognostic markers in breast cancer.

KEYWORDS:

DNA methylation; DNA sequencing; RNA sequencing; RRBS; breast cancer; chromosome X; differential gene expression; differential methylation; patient survival

PMID:
26039248
DOI:
10.2217/epi.15.43
[Indexed for MEDLINE]
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