LINE1 and Alu repetitive element DNA methylation in tumors and white blood cells from epithelial ovarian cancer patients

Stacey N. Akers, Kirsten Moysich, Wa Zhang, Golda Collamat Lai, Austin Miller, Shashikant Lele, Kunle Odunsi, Adam R. Karpf

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Objective We determined whether DNA methylation of repetitive elements (RE) is altered in epithelial ovarian cancer (EOC) patient tumors and white blood cells (WBC), compared to normal tissue controls. Methods Two different quantitative measures of RE methylation (LINE1 and Alu bisulfite pyrosequencing) were used in normal and tumor tissues from EOC cases and controls. Tissues analyzed included: i) EOC, ii) normal ovarian surface epithelia (OSE), iii) normal fallopian tube surface epithelia (FTE), iv) WBC from EOC patients, obtained before and after treatment, and v) WBC from demographically-matched controls. Results REs were significantly hypomethylated in EOC compared to OSE and FTE, and LINE1 and Alu methylation showed a significant direct association in these tissues. In contrast, WBC RE methylation was significantly higher in EOC cases compared to controls. RE methylation in patient-matched EOC tumors and pre-treatment WBC did not correlate. Conclusions EOC shows robust RE hypomethylation compared to normal tissues from which the disease arises. In contrast, RE are generally hypermethylated in EOC patient WBC compared to controls. EOC tumor and WBC methylation did not correlate in matched patients, suggesting that RE methylation is independently controlled in tumor and normal tissues. Despite the significant differences observed over the population, the range of RE methylation in patient and control WBC overlapped, limiting their specific utility as an EOC biomarker. However, our data demonstrate that DNA methylation is deranged in normal tissues from EOC patients, supporting further investigation of WBC DNA methylation biomarkers suitable for EOC risk assessment.

Original languageEnglish (US)
Pages (from-to)462-467
Number of pages6
JournalGynecologic Oncology
Volume132
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Alu
  • DNA methylation
  • Epithelial ovarian cancer
  • LINE1
  • Repetitive elements

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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