Fig. 4: Intratumoral heterogeneity of DNA methylation profiles.

a Unsupervised hierarchical clustering of 5000 most variable probes in CpG islands of the genome in 68 subjects. Different tumors are indicated by different colors in the column sidebar, with normal samples colored in gray. The numbers in parenthesis are the number of normal tissue samples for the ‘normal’ group, or the number of tumor samples in each patient. The beta values represent estimates of methylation levels, with 0 being unmethylated and 1 fully methylated. b Distribution of ITH of DNA methylation in different genomic contexts. TSS 1500: 200–1500 bases upstream of the transcription start sites (TSS), TSS 200: 0–200 bases upstream of the TSS. 5′UTR: Within the 5′ untranslated region, between the TSS and the ATG start site. Gene body: Between the ATG and stop codon. 3′UTR: From the stop codon to poly A tail. Island: CpG island. Shore: 0–2 kb from island. Shelf: 2–4 kb from island. North: upstream (5′) of island. South: downstream (3′) of island. c ITH of DNA methylation in oncogenes (n = 176), tumor suppressor genes (n = 223) and other genes (n = 12,837). The p-values are based on unpaired two-sided t-test of the two groups indicated by arrows. The center line in the box plots indicates median APITH. The box length indicates the interquartile range (IQR). The whiskers extend to the largest and smallest APITH at most 1.5*IQR.