Figure 3: Inter and intratumour heterogeneity of syCRCs.

(a) Method to rebuild the clone composition of a tumour. Allele frequency of each somatic alteration is corrected for the tumour content and used to infer the alteration clonality. The density distributions of clonality for each type of alteration recapitulate the tumour clone composition (monoclonal, if the majority of alterations has clonality >80%; biclonal, if alterations accumulate between 35 and 80% clonality; or polyclonal if they have <35% clonality). (b) Clone composition of the 20 syCRCs as inferred from the clonality of their somatic alterations. (c) Clonality of putative driver alterations in EGFR and in other six genes known or suspected to give resistance to anti-EGFR therapy. Data are shown in both lesions of all patients, except UH2 because neither tumour from this patient showed alterations in the EGFR pathway. (d) Density distributions of clonality for somatic alterations in the two tumours of patient S6. Dots represent alterations in CRC genes as collected from the Network of Cancer Genes⁶¹.