Association between Long Interspersed Nuclear Element-1 Methylation and Relative Telomere Length in Wilms Tumor

Abstract

Background: DNA hypomethylation of long interspersed nuclear elements-1 (LINEs-1) occurs during carcinogenesis, whereas information addressing LINE-1 methylation in Wilms tumor (WT) is limited. The main purpose of our study was to quantify LINE-1 methylation levels and evaluate their relationship with relative telomere length (TL) in WT. Methods: We investigated LINE-1 methylation and relative TL using bisulfite-polymerase chain reaction (PCR) pyrosequencing and quantitative PCR, respectively, in 20 WT tissues, 10 normal kidney tissues and a WT cell line. Significant changes were analyzed by t-tests. Results: LINE-1 methylation levels were significantly lower (P < 0.05) and relative TLs were significantly shorter (P < 0.05) in WT compared with normal kidney. There was a significant positive relationship between LINE-1 methylation and relative TL in WT (r = 0.671, P = 0.001). LINE-1 Methylation levels were significantly associated with global DNA methylation (r = 0.332, P < 0.01). In addition, relative TL was shortened and LINE-1 methylation was decreased in a WT cell line treated with the hypomethylating agent 5-aza-2′-deoxycytidine compared with untreated WT cell line. Conclusion: These results suggest that LINE-1 hypomethylation is common and may be linked to telomere shortening in WT.

Keywords

• 5-aza-2′-deoxycytidine; Hypomethylation; Long Interspersed Nuclear Element-1; Relative Telomere Length; Wilms Tumor