Although aneuploidy (an abnormal chromosome content) was recognized as a hallmark of cancer cells more than a hundred years ago, uncertainty still exists on the exact cause(s) of this phenomenon. In recent years, researchers worldwide have revealed a great amount of insight into the processes that ensure the fidelity of chromosome segregation, leading to novel hypotheses on the origins of aneuploidy in cancer. In this special issue, leading experts in the field review a variety of timely topics that are highly relevant to our current understanding of (in)correct chromosome segregation. Emphasis in these reviews is on the most recent progress made in our conception of the mechanisms underlying correct chromosome segregation. The selected topics cover the fundamental aspects of chromosome cohesion, chromosome misattachment and missegregation, timely protein degradation in mitosis, as well as the mechanisms underlying coordination of chromosome segregation and cytokinesis. In addition, the contribution of centrosomes and the spindle assembly checkpoint to correct chromosome segregation will be discussed. Based on this knowledge, various routes to aneuploidy will be considered, such as checkpoint malfunction, chromosome missegregation, centrosome aberrancies and tetraploidization. The evidence supporting these distinct scenarios will be presented.
René H. Medema, PhD Professor of Experimental Oncology
Department of Medical Oncology
University Medical Center
Utrecht, The Netherlands
René Medema received his degree in Chemistry (1989) at the University of Leiden, The Netherlands. He obtained his Ph.D. from the University of Utrecht (1993) with a thesis on “p21ras and insulin signal transduction”. He has worked in the cell cycle field since his postdoctoral training in the laboratory of Dr. R.A. Weinberg (Whitehead Institute, Cambridge, MA). His work as an independent group leader has focused on transcriptional regulation of the cell cycle, and the function of cell cycle checkpoints. His group has uncovered the essential contribution of forkhead transcription factors FoxO and FoxM1 to cell cycle control. Also, his group has made major contributions to our understanding of the role of Polo-like kinase-1, the chromosome passenger complex and components of the spindle assembly checkpoint to proper chromosome segregation. Recently, his group has developed a particular interest in spindle assembly and checkpoint recovery. Professor Medema currently heads the Laboratory of Experimental Oncology at the University Medical Center Utrecht in the Netherlands. He received a prestigious VICI-grant for his work on mitotic checkpoints (2003) and was elected EMBO-member in 2007.
