Tissue of origin determines promoter hypermethylation patterns in cancers. (a) Cancer type determines tumor methylation profiles. Shown are heatmaps of methylation levels at the 1,009 hypermethylation prone genes in 7 tumor types. Genes are ordered by their frequency of methylation in breast cancer and tumors by the number of methylated genes. The black tick marks adjacent to the heatmaps indicate genes that are never methylated in that tumor type. (b) Most variation between tumors corresponds to levels of methylation at hypermethylation prone genes. Shown is a scatter plot of the median methylation level at the 1,009 methylation prone genes in each of the 1,149 tumors against its value along the first principal component. Tumors are colored by type. The two values are significantly correlated (R = -0.90, P < 2 × 10-16). (c) Tumor type specific components exist in tumor hypermethylation patterns. Shown is a three-dimensional scatter plot of the values of each of the 1,149 tumors along the 2nd, 3rd and 4th principal components. Tumors are colored by type (as in (b)).