1. Polyploidy, Aneuploidy and the Evolution of Cancer.................. 1 Lauren M. F. Merlo, Li?san Wang, John W. Pepper, Peter S. Rabinovitch and Carlo C. Maley Abstract.................... 1 Introduction................... 1 The Tetraploidy to Aneuploidy Progression in Carcinogenesis................. 1 Tetraploidy and Aneuploidy in Barrett's Esophagus................ 2 Not All Aneuploids Are Equal................. 4 Why Do Cancer Cells Survive with Such Massive Alterations to Their Genome?......... 5 Why Is Aneuploidy Common in Neoplastic Progression?................. 7 DNA Damage Sensing by Linkage................ 10 Ancient and Recent Cancer Genes............... 10 Conclusion................... 10 2. Molecular Mechanisms and Function of the Spindle Checkpoint, a Guardian of the Chromosome Stability................. 15 Daisuke Ito and Tomohiro Matsumoto Abstract................... 15 Introduction................. 15 Bipolar Attachment and Chromosome Congression............... 16 Molecular Basis of the Spindle Checkpoint.................. 17 Activation of the Spindle Checkpoint Signaling................... 19 Mad2 Template Model................ 20 Phosphorylation and Spindle Checkpoint Function............. 21 Silencing the Spindle Checkpoint.................. 22 Additional Surveillance System.................. 22 A Trigger of Tumorigenesis.................. 24 Conclusion.................. 24 3. Understanding Cytokinesis Fa ilure............... 27 Guillaume Normand and Randall W. King Abstract.................. 27 Cytokinesis Occurs in Multiple Stages................. 27 Stage I. Positioning the Division Plane and Initiating Cytokinesis.................... 28 Stage II. Ingression of the Cleavage Furrow............... 30 Stage II. Formation of the Midbody................ 34 Stage IV. Abscission.................. 35 Regulation of Cytokinesis............. 38 Coupling of Cytokinesis to Other Cellular Pathways............... 42 Conclusion................ 43 4. DNADamage and Polyploidization................ 57 Jeremy P.H. Chow and Randy Y.C. Poon Abstract .............. 57 Polyploidization and Cancer................. 57 Mechanisms of Polyploidization................. 58 The DNA Damage Checkpoints................. 60 Polyploidization Induced by DNA Damage................... 62 The Sensitivity of Polyploid Cells to DNA Damage................. 64 Polyploidization and Cancer Therapies................. 64 Conclusion................. 65 5. Role of the p53 Fa mily in Stabilizing the Genome and Preventing Polyploidization............... 73 Flaminia Talos and Ute M. Moll Abstract.............. 73 p53-Tumor Suppressor.............. 73 p53 and Genomic Stability............... 74 Introduction to p73.............. 78 p73 Functions................... 79 The Role of p73 in Genomic Stability................. 80 Conclusion.................... 86 6. Centrosomes, Polyploidy and Cancer................. 93 Anette Duensing and Stefan Duensing Abstract.................. 93 Introduction................ 93 The Centrosome Duplication Cycle.................. 94 Aberrant Centrosome Numbers in Cancer Cells..................... 94 Multiple Pathways Can Lead to Aberrant Centrosome Numbers: Studies Using Human Papillomavirus (HPV) Oncoproteins..................... 95 Mechanisms of Centrosome Amplification in Tumor Cells.................. 96 Aberrant Centrosome Numbers as a Consequence of Polyploidy-Implications for Genomic Instability in Cancer............... 99 Aberrant Centrosome Numbers as a Cause of Polyploidy.................. 100 Conclusion...................... 101 7. Polyploidy: Mechanisms and Cancer Promotion in Hematopoietic and Other Cells................ 105 Hao G. Nguyen and Katya Ravid Abstract.................. 105 Overview: Characteristics of Polyploidy and Its Induction Under Different Conditions ..................... 105 Prevalence of Polyploidy/Aneuploidy in Different Cancers.................. 107 Cancer Theories: Potential Involvement
