HYPOMETHYLATION OF L1 LINE SEQUENCES PREVAILING IN HUMAN UROTHELIAL CARCINOMA

Alterations of DNA methylation were investigated in 6 urothelial carci noma cell lines and 13 tumor tissues, The methylation of LI LINE seque nces was diminished in all cell lines (by 26 +/- 5%; range, 11-49%) an d in most tumors (by 21 +/- 5%; range, 0-60%) compared to normal bladd er mucosa, Hypermethylation of the calcitonin gene CpG island was rest ricted to cell lines and was not found in primary tumors, suggesting i t had arisen during culture. In single-cell clones of a urothelial car cinoma cell line, both hypomethylation of L1 sequences and hypermethyl ation of the calcitonin gene persisted, indicating that they coexist w ithin one cell, DNA methyltransferase expression did not correlate wit h the methylation status of the cell lines, but rather with histone H3 expression, Accordingly, it was down-regulated in quiescent cells, Ab errant expression of DNA methyltransferase is therefore not likely the cause for altered methylation patterns in urothelial carcinoma. L1 LI NE hypomethylation seems to prevail in urothelial carcinoma and in thi s tumor might be useful for diagnostic or prognostic purposes.