Origins and consequences of centrosome aberrations in human cancers

Recent years have seen a revival of interest in the possible contribution of centrosomes to the development of human cancers. The underlying hypothesis, formulated almost 100 years ago (Boveri T. The origin of malignant tumors; Baltimore, MD: Williams and Wilkins, 1929.), states that numerical and/or structural centrosome abnormalities will cause chromosome [corrected] missegregation. In addition, centrosome abnormalities are expected to affect cell shape, polarity, and motility. Thus, deregulation of centrosome number and function may foster both chromosomal instability and loss of tissue architecture--2 of the most common phenotypes associated with solid human tumors. In support of the role of centrosome deregulation in tumorigenesis, centrosome aberrations have been observed in early, premalignant lesions. Moreover, they are frequent in many different types of common tumors and their prominence often correlates with poor clinical outcome. This review addresses the origins of centrosome aberrations in human tumors as well as the expected impact of centrosome aberrations on cell fate and tumor development.