Polyclonal Structure of Intestinal Adenomas in ApcMin/+ Mice with Concomitant Loss of Apc+from all Tumor Lineages

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 25; pp. 13927 - 13931
• Main Authors: Merritt, A. J., Gould, K. A., Dove, W. F.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 09-12-1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Adenoma; Adenomatous Polyposis Coli - genetics; Adenomatous Polyposis Coli - pathology; Adenomatous Polyposis Coli Protein; Alleles; Animals; Antibodies; Biological Sciences; Chimera - genetics; Chimeras; Clone Cells - pathology; Crypts; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Digestive system; Female; Genes, APC; Genetic mutation; Genotype; Histology; Humans; Immunohistochemistry; Large intestine; Loss of Heterozygosity; Male; Medical research; Mice; Mice, Mutant Strains; Models, Genetic; Mosaicism; Mutation; Rodents; Small intestine; Tumors
• ISSN: 0027-8424; 1091-6490

When tumors form in intestinal epithelia, it is important to know whether 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 that belong to separate somatic clones within the epithelium. The clonality of early tumors has been investigated in mice with an inherited predisposition to intestinal tumors. Analysis of Min (multiple intestinal neoplasia) mice chimeric for a ubiquitously expressed cell lineage marker revealed that normal intestinal crypts are monoclonal, but intestinal adenomas frequently have a polyclonal structure, presenting even when very small as single, focal adenomas composed of at least two somatic lineages. Furthermore, within these polyclonal adenomas, all tumor lineages frequently lose the wild-type Apc allele. These observations can be interpreted by several models for clonal interaction within the epithelium, ranging from passive fusion within regions of high neoplastic potential to a requirement for active clonal cooperation.