Fig. 2.

On the Road to Intratumoral Heterogeneity: Centrosome amplification (CA), in conjunction with mechanisms that ensure mitotic clustering of supernumerary centrosomes, is a key driver of chromosomal instability (CIN) in tumors. Centrosome clustering also allows the tumor to navigate the perils that accompany the presence of excess centrosomes. CIN is the essential vehicle that allows the tumor to reach its goal of generating enough intratumoral heterogeneity (ITH) to handle selection pressures and allow the development of aggressive tumor phenotypes. The propensity of proliferative cells in a tumor to undergo frequent error-prone mitoses is termed Mitotic Propensity and constitutes the vital engine that powers the vehicle of CIN and propels it toward ITH.