Epigenomic analysis of Alu repeats in human ependymomas

Hehuang Xie*, Min Wang, Maria De F. Bonaldo, Veena Rajaram, Wendy Stellpflug, Christina Smith, Kelly Arndt, Stewart Goldman, Tadanori Tomita, Marcelo B. Soares

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Global loss of DNA methylation has been known for decades as an epigenomic aberration associated with carcinogenesis and cancer progression. Loss of DNA methylation affects predominantly repetitive elements, which encompass >50% of the CpG dinucleotides present in the human genome. Because of the lack of an effective approach, no studies have been conducted to reveal such genome-wide methylation changes at a single-base resolution. To precisely determine the CpG sites with methylation loss during progression of pediatric intracranial ependymomas, we exploited a high-throughput bisulfite sequencing approach that simultaneously generates methylation profiles for thousands of Alu elements and their flanking sequences. Comparison of the methylation profiles of normal and tumor tissues revealed that the methylation status of the majority of CpG sites adjacent to or within Alu repeats remain unaltered, while a small set of CpG sites gain or lose methylation in ependymomas. Compared to the CpG sites with stable methylation level between normal control and ependymomas, the differentially methylated CpG sites are enriched in the sequences with low CpG density in the flanking regions of Alu repeats, rather than within the Alu sequences themselves. In addition, the CpG sites that are hypermethylated in ependymomas are proximal to CpG islands, whereas those that are hypomethylated are overrepresented in intergenic regions. Lastly, aberrant methylation of several genomic loci was confirmed to be associated with the aggressive primary tumors and the relapsed ependymomas.

Original languageEnglish (US)
Pages (from-to)6952-6957
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - Apr 13 2010


  • Bisulfite sequencing
  • DNA methylation
  • Pediatric brain tumor

ASJC Scopus subject areas

  • General


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