Quantitative evidence for early metastatic seeding in colorectal cancer

Both the timing and molecular determinants of metastasis are unknown, hindering treatment and prevention efforts. Here we characterize the evolutionary dynamics of this lethal process by analyzing exome sequencing data from 118 biopsies from 23 colorectal cancer (CRC) patients with metastases to the liver or brain. The data show low primary tumor-metastasis genomic divergence, where canonical driver genes were acquired early. Analysis within a spatial tumor growth model and statistical inference framework indicates that early disseminated cells commonly (81%, 17/21 evaluable patients) seed metastases while the carcinoma is clinically undetectable (typically
Editorial summary: Analysis of evolutionary dynamics of colorectal cancers and paired distant brain or liver metastases provides evidence that early disseminated cancer cells seed metastases before the carcinoma is clinically undetectable.