title: 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.
authors.affiliation: The Ludwig Center for Cancer Genetics and Therapeutics, Department of Biostatistics, Howard Hughes Medical Institute, and Sidney Kimmel Cancer Center at The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Siân
authors.initials: S
authors.lastname: Jones
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Chen
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
authors.forename: Frank
authors.initials: F
authors.lastname: Diehl
authors.forename: Niko
authors.initials: N
authors.lastname: Beerenwinkel
authors.forename: Tibor
authors.initials: T
authors.lastname: Antal
authors.forename: Arne
authors.initials: A
authors.lastname: Traulsen
authors.forename: Martin A
authors.initials: MA
authors.lastname: Nowak
authors.forename: Christopher
authors.initials: C
authors.lastname: Siegel
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Joseph
authors.initials: J
authors.lastname: Willis
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D004247:DNA / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D023041:Xenograft Model Antitumor Assays
chemical_list: D004247:DNA