Table 1.
Overview of the sample composition and tumour characteristics within each of the four Consensus Clusters derived from genome-wide DNA methylation profiling of six CRC subtypes (reference groups)
| Consensus cluster 1 | Consensus cluster 2 | Consensus cluster 3 | Consensus cluster 4 | |
|---|---|---|---|---|
| Number of CRCs | 20 | 3 | 9 | 6 |
| Age at CRC diagnosis (mean ± s.d) | 38.7 ± 10.6 | 45.9 ± 12.8 | 65.5 ± 9.65 | 39.2 ± 11.3 |
| MLH1 promoter methylationa (mean ± s.d) | 0.076 ± 0.02 | 0.082 ± 0.02 | 0.548 ± 0.089 | 0.761 ± 0.045 |
| CIMPb (% positive) | 0 (0%) | 1 (33%) | 9 (100%) | 0 (0%) |
| Mean methylation across the VM-CpGsc | 0.32 | 0.42 | 0.45 | 0.35 |
| Lynch syndrome (n = 9) | 8 | 1 | 0 | 0 |
| MMR-proficient CRC (n = 9) | 8 | 1 | 0 | 0 |
| Double somatic MMR mutation CRC (n = 5) | 4 | 1 | 0 | 0 |
| Sporadic MLH1 methylated CRCs (n = 9) | 0 | 0 | 9 | 0 |
| MLH1 primary epimutation (n = 5) | 0 | 0 | 0 | 4 |
| MLH1 secondary epimutation (n = 1) | 0 | 0 | 0 | 2 |
aMean methylation (β-values) across the regulatory C region of MLH1
bCIMP was determined by the methylation levels of CpG probes overlapping five previously defined genes [40]
cMean methylation levels across the 77,113 most variably methylated CpGs (VM-CpGs), which was used for defining the Consensus Clusters. s.d.—standard deviation, VM-CpGs—(77,113) variably methylated CpGs defined by having high variation in the methylation patterns as ranked by standard deviation across 38 reference CRCs