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Title: Correlation of LINE-1 methylation levels in patient-matched buffy coat, serum, buccal cell, and bladder tumor tissue DNA samples.
Authors: van Bemmel D,  Lenz P,  Liao LM,  Baris D,  Sternberg LR,  Warner A,  Johnson A,  Jones M,  Kida M,  Schwenn M,  Schned AR,  Silverman DT,  Rothman N,  Moore LE
Journal: Cancer Epidemiol Biomarkers Prev
Date: 2012 Jul
Branches: OEEB
PubMed ID: 22539607
PMC ID: PMC3397796
Abstract: BACKGROUND: Evidence suggests that global methylation levels in blood cell DNA may be a biomarker for cancer risk. To date, most studies have used genomic DNA isolated from blood or urine as a surrogate marker of global DNA methylation levels in bladder tumor tissue. METHODS: A subset of 50 bladder cancer cases was selected from the New England Bladder Cancer Case-Control Study. Genomic DNA was isolated from buffy coat, buccal cells, serum, and formalin-fixed, paraffin-embedded tissue for each participant. DNA methylation at four CpG sites within the long interspersed nucleotide element (LINE-1) repetitive element was quantified using pyrosequencing and expressed as a mean methylation level across sites. RESULTS: Overall, the mean percent (%) LINE-1 5-methylcytosine (%5MeC) level was highest in serum (80.47% ± 1.44%) and lowest in bladder tumor DNA (61.36% ± 12.74%) and levels varied significantly across tissue types (P = 0.001). An inverse association between LINE-1 mean %5MeC and tumor stage (P = 0.001) and grade (P = 0.002) was observed. A moderate correlation between patient-matched serum and buffy coat DNA LINE-1 %5MeC levels was found (r = 0.32, P = 0.03) but levels were uncorrelated among other matched genomic DNA samples. CONCLUSIONS: The mean promoter LINE-1 %5MeC measurements were correlated between buffy coat and serum DNA samples. No correlation was observed between genomic DNA sources and tumor tissues; however a significant inverse association between tumor percent LINE-1 methylation and tumor stage/grade was found. IMPACT: LINE-1 methylation measured in case blood DNA did not reflect that observed in bladder tumor tissue but may represent other factors associated with carcinogenesis.