Figure 3
Association between levels of long interspersed nuclear element-1 (LINE-1) methylation and chromosomal aberrations in malignant melanoma (MM). (A) comparison of LINE-1 methylation levels between MMs with and without loss of (left) 13q (n = 28 and 39, respectively) and (right) any chromosome arm (n = 36 and 31, respectively). Each dot represents the level of LINE-1 methylation in a single tumor. The average methylation levels and P values are shown underneath. (B) Volcano plot showing the relationship between changes in LINE-1 methylation and chromosomal aberrations. Each dot represents a chromosomal arm. Differences in the average levels of LINE-1 methylation between tumors with and without aberrations in the indicated chromosomal arms (loss in green and gain in red) are plotted on the horizontal axis, and P values for the respective comparisons are plotted on the vertical axis. Chromosomal arms in which loss exhibited a significant association with LINE-1 hypomethylation (P < 0.05) are highlighted. (C) Scatter plots showing the correlations between the numbers of array comparative genomic hybridization (aCGH) probes in the gained or lost regions and LINE-1 methylation levels in MMs, with regression lines and their 95% confidence intervals. Note that the numbers of probes in the lost regions showed a significant inverse correlation with the LINE-1 methylation levels. (D) Schematic diagram of the putative breakpoints. Green lines indicate aCGH probe sets within lost regions, while blue lines indicate those within intact genomic regions. Light green and light blue areas represent lost and intact genomic regions, respectively. Breakpoints (pink) were defined as regions encompassed by a pair of probe sets located at the boundary of the genomic lost regions. (E) Scatter plot showing the correlations between the numbers of breakpoints and LINE-1 methylation levels in MMs, with the regression line and its 95% confidence interval. Note that the numbers of breakpoints showed a significant inverse correlation with the LINE-1 methylation levels. (F) Frequencies of the indicated LINE-1 densities (0, 0.01 to 13.43, 13.44 to 26.35, 26.36 to 39.99 and ≥40.00 per 100,000 bp) at the common breakpoints (CBPs, n = 80) and across the whole genome. Note that CBPs were significantly associated with higher LINE-1 densities.