Comparative lesion sequencing provides insights into tumor evolution

Abstract

We show that the times separating the birth of benign, invasive, and metastatic tumor cells can be determined by analysis of the mutations they have in common. When combined with prior clinical observations, these analyses suggest the following general conclusions about colorectal tumorigenesis: ( i ) It takes ≈17 years for a large benign tumor to evolve into an advanced cancer but <2 years for cells within that cancer to acquire the ability to metastasize; ( ii ) it requires few, if any, selective events to transform a highly invasive cancer cell into one with the capacity to metastasize; ( iii ) the process of cell culture ex vivo does not introduce new clonal mutations into colorectal tumor cell populations; and ( iv ) the rates at which point mutations develop in advanced cancers are similar to those of normal cells. These results have important implications for understanding human tumor pathogenesis, particularly those associated with metastasis.

Keywords

Affiliated Institutions

• University Hospitals of Cleveland US
• Board of the Swiss Federal Institutes of Technology CH
• Harvard University US
• Sidney Kimmel Cancer Center US
• Johns Hopkins University US
• Max Planck Institute for Evolutionary Biology DE
• Howard Hughes Medical Institute US
• Cancer Genetics (United States) US
• ETH Zurich CH

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