title: LINE1 and Alu repetitive element DNA methylation in tumors and white blood cells from epithelial ovarian cancer patients.
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.
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Stacey N
authors.initials: SN
authors.lastname: Akers
authors.affiliation: Department of Cancer Prevention and Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Moysich
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA; Eppley Institute, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Wa
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Golda
authors.initials: G
authors.lastname: Collamat Lai
authors.affiliation: Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Miller
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA; Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA; Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA; Eppley Institute, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: adam.karpf@unmc.edu.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Karpf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020087:Alu Elements; D000077216:Carcinoma, Ovarian Epithelial; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D020084:Long Interspersed Nucleotide Elements; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000235:genetics*; D018570:Risk Assessment
keywords: Alu; DNA methylation; Epithelial ovarian cancer; LINE1; Repetitive elements