Fig. 1

Genome-wide DNA methylation profiling of brain tumors. a Diagram describing the normalization algorithm of Infinium HM450K probes. b Matrix depicting the Spearman’s ρ correlation coefficients among primary and metastatic brain tumors. c Principal component analysis (PCA) of GBM (n = 60) and brain metastases (n = 94) using DNA methylation level of 22,483 randomly-selected genomic regions. d DNA methylation level of the 12 most differentially methylated regions between GBM and BM specimens. The upper panel shows the β-value of six genomic regions differentially hypermethylated in BM (cg07076109, cg19111287, cg09962377, cg10982851, cg15002250, and cg23108580) and the lower panel shows the β-value of six genomic regions differentially hypermethylated in GBM (cg25814383, cg26306329, cg06663644, cg20604286, cg04314308, and cg26306994) for each specimen in the study (n = 154). The top and bottom of each box represent the first and third quartile, respectively; the internal line represents the median. e Validation of differentially methylated regions by qMSP in an independent cohort of brain tumor specimens (n = 72). The left boxplot shows the methylation level of a genomic region hypermethylated in BM specimens (BM-C; cg09962377) and the right boxplot the level of a genomic region hypermethylated in GBM specimens (GBM-A; cg25814383; chr19:19,336,240). The top and bottom of each box represent the first and third quartile, respectively; the internal line represents the median. *Wilcoxon test, P-value < 0.02. f ROC showing the prediction potential of brain tumor type using qMSP scores for each independent genomic region and score for the combination (DNAm level of BM-C minus DNAm level of GBM-A; AUC = 0.92, 95% CI = 0.85-0.99); see Supplementary Data 3 for details about validated genomic regions. The AUC values are indicated between square brackets