Stacey N Akers1, Kirsten Moysich2, Wa Zhang3, Golda Collamat Lai4, Austin Miller5, Shashikant Lele1, Kunle Odunsi6, Adam R Karpf7. 1. Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA. 2. Department of Cancer Prevention and Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA. 3. 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. 4. Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA. 5. Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY, USA. 6. 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. 7. 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.
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.
OBJECTIVE: We determined whether DNA methylation of repetitive elements (RE) is altered in epithelial ovarian cancer (EOC) patienttumors 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: Michelle L Kurta; Kirsten B Moysich; Joel L Weissfeld; Ada O Youk; Clareann H Bunker; Robert P Edwards; Francesmary Modugno; Roberta B Ness; Brenda Diergaarde Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-06-15 Impact factor: 4.254
Authors: Martin Widschwendter; Guanchao Jiang; Christian Woods; Hannes M Müller; Heidi Fiegl; Georg Goebel; Christian Marth; Elisabeth Müller-Holzner; Alain G Zeimet; Peter W Laird; Melanie Ehrlich Journal: Cancer Res Date: 2004-07-01 Impact factor: 12.701
Authors: Ashok Sharma; Mustafa Albahrani; Wa Zhang; Christina N Kufel; Smitha R James; Kunle Odunsi; David Klinkebiel; Adam R Karpf Journal: Epigenetics Date: 2019-03-04 Impact factor: 4.528