title: Clonal structure of carcinogen-induced intestinal tumors in mice.
abstract: Previous studies have shown that intestinal tumors from Apc(Min)(/+) (Min) mice and familial adenomatous polyposis (FAP) patients are often polyclonal. We sought to determine whether polyclonality is unique to tumors arising from hereditary predispositions or, instead, is a common feature of intestinal tumorigenesis in other pathways to tumorigenesis. Ethylnitrosourea-induced intestinal tumors from mice wild type at the Apc locus and chimeric for the Rosa26 lineage marker were analyzed. Many were overtly polyclonal, being composed of a mixture of Rosa26(+) and Rosa26(-) neoplastic cells. Statistical analyses revealed that polyclonality could be explained by interactions between two initiated clones separated by a very short distance. The frequency of overtly polyclonal tumors and the range of interactions estimated in this model are similar to those observed when analyzing familial tumors from Min mice. Thus, polyclonality does not depend on the familial pathway to tumorigenesis. Interactions between two initiated clones might provide a selective advantage during the early stages of intestinal tumorigenesis.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Thliveris
authors.forename: Linda
authors.initials: L
authors.lastname: Clipson
authors.forename: Alanna
authors.initials: A
authors.lastname: White
authors.forename: Jesse
authors.initials: J
authors.lastname: Waggoner
authors.forename: Lauren
authors.initials: L
authors.lastname: Plesh
authors.forename: Bridget L
authors.initials: BL
authors.lastname: Skinner
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Zahm
authors.forename: Ruth
authors.initials: R
authors.lastname: Sullivan
authors.forename: William F
authors.initials: WF
authors.lastname: Dove
authors.forename: Michael A
authors.initials: MA
authors.lastname: Newton
authors.forename: Richard B
authors.initials: RB
authors.lastname: Halberg
mesh_terms: D011125:Adenomatous Polyposis Coli; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D046528:Chimerism; D002999:Clone Cells; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D017491:Genes, APC / Q000502:physiology; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000145:classification* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D011506:Proteins / Q000502:physiology*; D022661:RNA, Untranslated
chemical_list: D002273:Carcinogens; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D011506:Proteins; D022661:RNA, Untranslated; D005038:Ethylnitrosourea