Rapid evolution and biogeographic spread in a colorectal cancer

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• We are able to identify a rapid and early metastatic spread and multiple migration events, where both primary tumor and metastases diversify in parallel.

• In metastatic colorectal cancer (mCRC) many aspects underlying the dissemination of cancer cells to tissues beyond primary lesions have been difficult to determine. Although earlier models of mCRC progression have proposed a sequential metastatic cascade, with cells from the primary tumor first escaping to local lymph nodes from where they seed distant tissues10, conflicting evidence has recently emerged, as some genomic datasets seem to favor an independent origin of distant and lymph node metastases

• All the metastatic lineages grouped together with high support, suggesting a monoclonal origin. The age of the tumor was estimated to be 6.94–6.45 years (95% Highest Posterior Density (HPD): 9.98/9.16–4.43/4.36) prior to clinical diagnosis (PCD

• Also, the results imply an early origin of the metastatic ancestor, 4.20 years PCD (95% HPD: 6.30–2.46)

• Our biogeographic reconstruction revealed a pattern of metastatic dissemination in which the primary tumor directly seeded liver metastases without an apparent early involvement of the lymphatic system.