POLYCLONAL STRUCTURE OF INTESTINAL ADENOMAS IN APC-(MIN) + MICE WITH CONCOMITANT LOSS OF APC(+) FROM ALL TUMOR LINEAGES/

When tumors form in intestinal epithelia, it is important to know whet her they involve single initiated somatic clones. Advanced carcinomas in humans and mice are known to be monoclonal. However, earlier stages of tumorigenesis may instead involve an interaction between cells tha t belong to separate somatic clones within the epithelium. The clonali ty of early tumors has been investigated in mice with an inherited pre disposition to intestinal tumors. Analysis of Min (multiple intestinal neoplasia) mice chimeric for a ubiquitously expressed cell lineage ma rker revealed that normal intestinal crypts are monoclonal, but intest inal adenomas frequently have a polyclonal structure, presenting even when very small as single, focal adenomas composed of at least two som atic lineages. Furthermore, within these polyclonal adenomas, all tumo r lineages frequently lose the wild-type Ape allele. These observation s can be interpreted by several models for clonal interaction within t he epithelium, ranging from passive fusion within regions of high neop lastic potential to a requirement for active clonal cooperation.