Author(s):Thliveris AT, Clipson L, White A, Waggoner J, Plesh L, Skinner BL, Zahm CD, Sullivan R, Dove WF, Newton MA, Halberg RB. Clonal structure of carcinogen-induced intestinal tumors in mice. Cancer Prev Res (Phila). 2011 Jun;4(6):916-23. doi: 10.1158/1940-6207.CAPR-11-0022. PMID 21636550
Journal: Cancer Prevention Research (Philadelphia, Pa.), Volume 4, Issue 6, Jun 2011
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.