Supplementary Figures S1-S17 from Negative Selection Maintains Grossly Altered but Broadly Stable Karyotypes in Metastatic Colorectal Cancer

Supplementary Figures 1-17 and Figure Legends Supplementary Figure 1: CNA subclonality decreases with progression within early colorectal cancers. Supplementary Figure 2: CNA subclonality assessed by different metrics. Supplementary Figure 3: Divergence decreases with progression within early colorectal. Supplementary Figure 4: Derivation of a simple genome doubling classifier. Supplementary Figure 5: Divergence is highest in subclonal and lowest in clonal genome doubled cases. Supplementary Figure 6: In situ analysis using FISH and DNAscope shows copy number instability at the single-cell level. Supplementary Figure 7: Simulations demonstrate stabilising selection suppresses karyotypic diversity when tumours are close to fitness peak. Supplementary Figure 8: The non-identifiability of the mutation rate (μ) and the strength of stabilising selection. Supplementary Figure 9: Cross-cohort study shows CNA subclonality, CNA burden and genome doubling change with progression. Supplementary Figure 10: Multi-site longitudinal karyotype phylogenetic assessment of individual CRC patients during tumour progression and drug treatment. Supplementary Figure 11: Multi-site longitudinal karyotype assessment of individual CRC patients during tumour progression and drug treatment (patients LM001 – LM0029). Supplementary Figure 12: Multi-site longitudinal karyotype assessment of individual CRC patients during tumour progression and drug treatment (patients LM0032 – LM0089). Supplementary Figure 13: Multi-site longitudinal karyotype assessment of individual CRC patients during tumour progression and drug treatment (patients LM0095 – LM0139). Supplementary Figure 14: Number of phylogenetic copy number events and proportion of the aberrant genome subclonal correlate in carcinomas. Supplementary Figure 15: Patterns of aneuploidy evolution during metastatic spread and treatment. Supplementary Figure 16: Recurrent CNAs are similar between the primary and metastatic lesions. Supplementary Figure 17: Early colorectal cancer and primary tumour samples from metastatic patients show similar CNA recurrence and number of segments, but not PGA.