Figure 6. Transient 5-AZA-CdR treatment reduces the frequency of primary colorectal CICs independent of CIMP status, and this activity is dependent on MAVS activation.

A) Colorectal patient-derived cells were classified accordingly their CpG Island Methylator Phenotype (CIMP) into CIMP^high (Sample 92), CIMP^low (Sample 181) and non-CIMP (Sample 73). Primary tissue DNA methylation data and CIMP classification were obtained from (Hinoue et al., 2012). Heatmap shows the pairwise correlation using Spearman correlation method of each sample. B, D and F) Frequency of colorectal CICs before and after low dose transient 5-AZA-CdR treatment measured by in-vitro limiting dilution assay in MAVS wild type cells. Patient-derived cells obtained from a CIMP^high (sample 92) (B), a CIMP^low (sample 181) (D) and a non-CIMP (sample 73) (F) were used. C, E and G) Frequency of colorectal CICs before and after low dose transient 5-AZA-CdR treatment measured by in-vitro limiting dilution assay in MAVS knocked-down (shMAVS) cells. Patient-derived cells obtained from a CIMP^high (sample 92) (C), a CIMP^low (sample 181) (E) and a non-CIMP (sample 73) (G) were used. The y-axis denotes the confidence intervals (lower, estimate and upper) for CIC frequency. Pairwise chi-squared test was used to test for difference in CIC frequency. See also Figure S6.