Degree and site of chromosomal instability define its oncogenic potential

Most human cancers are aneuploid due to a chromosomal instability (CIN) phenotype, yet the roles of CIN and aneuploidy in tumor formation remain unclear from animal studies. Using a conditional mouse model that enables tissue-specific induction of graded CIN, we show that a particular range of CIN is sufficient to drive very early spontaneous adenoma formation in the intestine. In ApcMin/+ mice, moderate CIN markedly increases adenoma burden throughout the intestinal tract, especially in the distal colon, recapitulating human disease patterns. Notably, an even higher CIN level further promotes adenoma formation in the distal colon but has no effect in the small intestine. Thus, CIN can be potently oncogenic, with oncogenic potential determined by both the degree of CIN and the tissue context.

Wilma H.M. Hoevenaaar, Aniek Janssen, Ajit I. Quirindongo, Huiying Ma, Sjoerd J. Klaasen, Antoinette Teixeira, Bastian van Gerwen, Nico LansUID, Folkert H.M. Morsink, G. Johan A. Offerhaus, René H. Medema, Geert J.P.L. Kops, Nannette Jelluma