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

Hypomethylation of DNA repetitive elements is it 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 anti 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 front four individuals undergoing autopsy, 34 paired normal and tumor tissues front 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 front 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 front 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 ire 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. (C) 2009 UICC