Changes in DNA methylation of tandem DNA repeats are different from interspersed repeats in cancer.

Hypomethylation of DNA repetitive elements is a common finding in cancer, but very little is known about the DNA methylation changes of different types of DNA repetitive elements, such as interspersed repeats (LINE1 and Alu Yb8) and tandem repeats (Sat-alpha, NBL-2 and D4Z4). We used bisulfite-PCR Pyrosequencing to quantitatively measure the DNA methylation of five different DNA repetitive elements in normal tissue and cancer. In all we studied 10 different tissues from four individuals undergoing autopsy, 34 paired normal and tumor tissues from patients with bladder cancer, 58 patients with chronic myelogenous leukemia and 23 patients with acute promyelocytic leukemia. We found that the DNA methylation of interspersed repeats (LINE1 and Alu Yb8) was very consistent from person to person and tissue to tissue while tandem DNA repeats appeared more variable in normal tissues. In bladder cancer we found clear hypomethylation of LINE1, Alu Yb8, Sat-alpha and NBL-2. Conversely, we found an increase in the DNA methylation levels of D4Z4 from normal to cancer. In contrast leukemia showed no significant changes in the DNA methylation of LINE1 and Alu Yb8, but DNA methylation increases in NBL-2 and D4Z4 tandem repeats. Our findings show that the changes in DNA methylation levels of individual DNA repetitive elements are unique for each repetitive element, which may reflect distinct epigenetic factors and may have important implications in the use of DNA methylation of repetitive elements as global DNA methylation biomarkers.