Polyploidization and Cancer

1. Polyploidy, Aneuploidy and the Evolutionof Cancer.................. 1Lauren M. F. Merlo, Li?san Wang, John W. Pepper, Peter S. Rabinovitchand Carlo C. MaleyAbstract.................... 1Introduction................... 1The Tetraploidy to Aneuploidy Progression in Carcinogenesis................. 1Tetraploidy and Aneuploidy in Barrett’s Esophagus................ 2Not All Aneuploids Are Equal................. 4Why Do Cancer Cells Survive with Such Massive Alterations to Their Genome?......... 5Why Is Aneuploidy Common in Neoplastic Progression?................. 7DNA Damage Sensing by Linkage................ 10Ancient and Recent Cancer Genes............... 10Conclusion................... 102. Molecular Mechanisms and Function of the Spindle Checkpoint, a Guardian of the Chromosome Stability................. 15Daisuke Ito and Tomohiro MatsumotoAbstract................... 15Introduction................. 15Bipolar Attachment and Chromosome Congression............... 16Molecular Basis of the Spindle Checkpoint.................. 17Activation of the Spindle Checkpoint Signaling................... 19Mad2 Template Model................ 20Phosphorylation and Spindle Checkpoint Function............. 21Silencing the Spindle Checkpoint.................. 22Additional Surveillance System.................. 22A Trigger of Tumorigenesis.................. 24Conclusion.................. 243. Understanding Cytokinesis Fa ilure............... 27Guillaume Normand and Randall W. KingAbstract.................. 27Cytokinesis Occurs in Multiple Stages................. 27Stage I. Positioning the Division Plane and Initiating Cytokinesis.................... 28Stage II. Ingression of the Cleavage Furrow............... 30Stage II. Formation of the Midbody................ 34Stage IV. Abscission.................. 35Regulation of Cytokinesis............. 38Coupling of Cytokinesis to Other Cellular Pathways............... 42Conclusion................ 434. DNADamage and Polyploidization................ 57Jeremy P.H. Chow and Randy Y.C. PoonAbstract .............. 57Polyploidization and Cancer................. 57Mechanisms of Polyploidization................. 58The DNA Damage Checkpoints................. 60Polyploidization Induced by DNA Damage................... 62The Sensitivity of Polyploid Cells to DNA Damage................. 64Polyploidization and Cancer Therapies................. 64Conclusion................. 655. Role of the p53 Fa mily in Stabilizing the Genome and Preventing Polyploidization............... 73Flaminia Talos and Ute M. MollAbstract.............. 73p53-Tumor Suppressor.............. 73p53 and Genomic Stability............... 74Introduction to p73.............. 78p73 Functions................... 79The Role of p73 in Genomic Stability................. 80Conclusion.................... 866. Centrosomes, Polyploidy and Cancer................. 93Anette Duensing and Stefan DuensingAbstract.................. 93Introduction................ 93The Centrosome Duplication Cycle.................. 94Aberrant Centrosome Numbers in Cancer Cells..................... 94Multiple Pathways Can Lead to Aberrant Centrosome Numbers: Studies Using Human Papillomavirus (HPV) Oncoproteins..................... 95Mechanisms of Centrosome Amplification in Tumor Cells.................. 96Aberrant Centrosome Numbers as a Consequence of Polyploidy-Implicationsfor Genomic Instability in Cancer............... 99Aberrant Centrosome Numbers as a Cause of Polyploidy.................. 100Conclusion...................... 1017. Polyploidy: Mechanisms and Cancer Promotion in Hematopoietic and Other Cells................ 105Hao G. Nguyen and Katya RavidAbstract.................. 105Overview: Characteristics of Polyploidy and Its Induction Under DifferentConditions ..................... 105Prevalence of Polyploidy/Aneuploidy in Different Cancers.................. 107Cancer Theories: Potential Involvement