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          Institute: MPI für Evolutionsbiologie     Collection: Evolutionary ecology     Display Documents



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ID: 361815.0, MPI für Evolutionsbiologie / Evolutionary ecology
Comparative lesion sequencing provides insights into tumor evolution
Authors:Jones, Siân; Chen, Wei-dong; Parmigiana, 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.
Language:English
Date of Publication (YYYY-MM-DD):2008-03-18
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Journal Abbrev.:PNAS
Volume:105
Issue / Number:11
Start Page:4283
End Page:4288
Review Status:not specified
Audience:Not Specified
Abstract / Description: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 approximate 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; (it) 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.
Free Keywords:cancer genetics; colorectal cancer; metastasis; stem cells
External Publication Status:published
Document Type:Article
Affiliations:MPI für Evolutionsbiologie/Abt. Evolutionsökologie
MPI für Evolutionsbiologie/AG Evolutionstheorie
External Affiliations:Johns Hopkins Med Inst, Howard Hughes Med Inst, Dept Biostat, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA; Johns Hopkins Med Inst, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA; Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA; Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA; Case Western Reserve Univ, Dept Surg, Cleveland, OH 44106 USA; Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA;
Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA
Howard Hughes Med Inst, Cleveland, OH 44106 USA; ETH, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland; Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA
Identifiers:ISSN:0027-8424 [ID-No:1]
DOI:10.1073/pnas.0712345105 [ID-No:2]
LOCALID:2609/S 38774 [Listen-Nummer/S-Nummer]
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