title: Chromosome X genomic and epigenomic aberrations and clinical implications in breast cancer by base resolution profiling.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Naresh
authors.initials: N
authors.lastname: Prodduturi
authors.affiliation: Medical School, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Sun
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: E Aubrey
authors.initials: EA
authors.lastname: Thompson
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jean-Pierre A
authors.initials: JP
authors.lastname: Kocher
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X / Q000737:chemistry / Q000378:metabolism*; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D016208:Databases, Factual; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016019:Survival Analysis; D059467:Transcriptome; D049951:X Chromosome Inactivation
chemical_list: D044503:5-Methylcytosine
keywords: DNA methylation; DNA sequencing; RNA sequencing; RRBS; breast cancer; chromosome X; differential gene expression; differential methylation; patient survival