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Comparative lesion sequencing provides insights into tumor evolution

Jones, Siân, Chen, Wei-dong, Parmigiani, Giovanni, Diehl, Frank, Beerenwinkel, Niko, Antal, Tibor, Traulsen, Arne, Nowak, Martin A., Siegel, Christopher, Velculescu, Victor E., Kinzler, Kenneth W., Vogelstein, Bert, Willis, Joseph, Markowitz, Sanford D.
Proceedings of the National Academy of Sciences of the United States of America 2008 v.105 no.11 pp. 4283-4288
carcinogenesis, cell culture, colorectal neoplasms, humans, metastasis, neoplasm cells, point mutation, population
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 [almost equal to]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.