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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 approximately 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.

SUBMITTER: Jones S 

PROVIDER: S-EPMC2393770 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Comparative lesion sequencing provides insights into tumor evolution.

Jones Siân S   Chen Wei-Dong WD   Parmigiani Giovanni G   Diehl Frank F   Beerenwinkel Niko N   Antal Tibor T   Traulsen Arne A   Nowak Martin A MA   Siegel Christopher C   Velculescu Victor E VE   Kinzler Kenneth W KW   Vogelstein Bert B   Willis Joseph J   Markowitz Sanford D SD  

Proceedings of the National Academy of Sciences of the United States of America 20080312 11

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 approximately 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 an  ...[more]