Fig. 2.

Epigenetic diversity in adenomatous crypts. (A) Topographical maps showing crypts sampled from adenoma 174 (wholly APC-mutant, KRAS-mutant subclone). A pairwise comparison of adenomatous crypts showed crypts had markedly different methylation patterns. Individual adenomatous crypts showed intracrypt epigenetic diversity. Boxes of dots represent methylation patterns; each row is a tag (molecule), each column a CpG site. An open circle denotes an unmethylated site; a filled circle denotes a methylated site. (B and C) Pairwise differences between each pair of crypts, sorted by adenoma. In some adenomas (e.g., 160 and 158), all crypts had similar methylation patterns, whereas in other adenomas (e.g., 162) some crypts had methylation patterns that were very different from those in the majority of crypts, illustrating the differences in the life-history of each adenoma. (B) ICD and (C) minimum distance between crypts. Colors indicate the dominant genotype within the adenoma; blue: APC–mutant KRAS–wild-type, red: APC/KRAS-mutant, green: APC/KRAS–wild-type).