title: Methylome-wide comparison of human genomic DNA extracted from whole blood and from EBV-transformed lymphocyte cell lines.
abstract: DNA from Epstein-Barr virus-transformed lymphocyte cell lines (LCLs) has proven useful for studies of genetic sequence polymorphisms. Whether LCL DNA is suitable for methylation studies is less clear. We conduct a genome-wide methylation investigation using an array set with 45 million probes to investigate the methylome of LCL DNA and technical duplicates of WB DNA from the same 10 individuals. We focus specifically on methylation sites that show variation between individuals and, therefore, are potentially useful as biomarkers. The sample correlations for the methylation variable probes ranged from 0.69 to 0.78 for the WB duplicates and from 0.27 to 0.72 for WB vs LCL. To compare the pattern of the methylation signals, we grouped adjacent probes based on their inter-correlations. These analyses showed ∼29 000 and ∼14 000 blocks in WB and LCL, respectively. Merely 31% of the methylated regions detected in WB were detectable in LCLs. Furthermore, we observed significant differences in mean difference between WB and LCL as compared with duplicates of WB (P-value =2.2 × 10(-16)). Our study shows that there are substantial differences in the DNA methylation patterns between LCL and WB. Thus, LCL DNA should not be used as a proxy for WB DNA in methylome-wide studies.
authors.affiliation: Center for Biomarker Research and Personalized Medicine, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA. kaaberg@vcu.edu
authors.forename: Karolina
authors.initials: K
authors.lastname: Åberg
authors.forename: Amit N
authors.initials: AN
authors.lastname: Khachane
authors.forename: Gábor
authors.initials: G
authors.lastname: Rudolf
authors.forename: Srilaxmi
authors.initials: S
authors.lastname: Nerella
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Fugman
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: Edwin J C G
authors.initials: EJ
authors.lastname: van den Oord
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002461:Cell Line, Transformed; D004247:DNA / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D019175:DNA Methylation; D015342:DNA Probes; D005260:Female; D056426:Genetic Loci; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity
chemical_list: D015415:Biomarkers; D015342:DNA Probes; D004247:DNA