Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 11, Pages 4283-4288Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0712345105
Keywords
cancer genetics; colorectal cancer; metastasis; stem cells
Categories
Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [CA120237, R01 CA127306, CA43460, P30 CA043703, R01 CA121113, R01 CA120237, CA62924, U54 CA116867, CA121113, R37 CA043460, CA57345, P50 CA062924, CA043703, CA127306, CA116867, R37 CA057345, R01 CA057345, R01 CA105090] Funding Source: Medline
- NIGMS NIH HHS [GM078986, R01 GM078986-02, R01 GM078986] Funding Source: Medline
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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.
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