摘要：SummaryTumor multiregion sequencing reveals intratumor heterogeneity (ITH) and clonal evolution playing a key role in tumor progression and metastases. Large-scale high-depth multiregional sequencing of colorectal cancer, comparative analysis among patients with right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer (RC), as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTDs) from evolutionary perspective remain weakly explored. Here, we recruited 68 patients with RCC (18), LCC (20), and RC (30). We performed high-depth whole-exome sequencing of 206 tumor regions including 176 primary tumors, 19 LN, and 11 ENTD samples. Our results showed ITH with a Darwinian pattern of evolution and the evolution pattern of LCC and RC was more complex and divergent than RCC. Genetic and evolutionary evidences found that both LN and ENTD originated from different clones. Moreover, ENTD was a distinct entity from LN and evolved later.Graphical abstractDisplay OmittedHighlights•Clonal evolution of colorectal tumors followed Darwinian pattern of evolution•Intratumor heterogeneity in patients with right-sided and left-sided colon and rectal cancer•Evolution of left-sided colon cancer and rectal cancer was more complex and divergent•Lymph node metastasis and extranodal tumor deposits were of polyclonal in originEvolutionary biology; Cancer systems biology; Genomics
