Genome Instability in Cancer Development (Advances in Experimental Medicine and Biology Book 570)

Research over the past decades has firmly established the genetic basis of cancer. In particular, studies on animal tumour viruses and chromosome rearrangements in human tumours have concurred to identify so-called ‘proto-oncogenes’ and ‘tumour suppressor genes’, whose deregulation promotes carcinogenesis. These important findings not only explain the occurrence of certain hereditary tumours, but they also set the stage for the development of anti-cancer drugs that specifically target activated oncogenes. However, in spite of tremendous progress towards the elucidation of key signalling pathways involved in carcinogenesis, most cancers continue to elude currently available therapies. This stands as a reminder that “cancer” is an extraordinarily complex disease: although some cancers of the haematopoietic system show only a limited number of characteristic chromosomal aberrations, most solid tumours display a myriad of genetic changes and considerable genetic heterogeneity. This is thought to reflect a trait commonly referred to as ‘genome instability’, so that no two cancers are ever likely to display the exact same genetic alterations. Numerical and structural chromosome aberrations were recognised as a hallmark of human tumours for more than a century. Yet, the causes and consequences of these aberrations still remain to be fully understood. In particular, the question of how genome instability impacts on the development of human cancers continues to evoke intense debate. The Problem Of Genome Instability -- The Multiplicity Of Mutations In Human Cancers / Ranga N. Venkatesan And Lawrence A. Loeb -- Monitoring Chromosome Rearrangements / Michael R. Speicher -- Dna Repair And Mutagenesis -- Nucleotide Excision Repair And Its Connection With Cancer And Ageing / Jaan-olle Andressoo, Jan H.j. Hoeijmakers And Harm De Waard -- Dna Mismatch Repair And Colon Cancer / Giancarlo Marra And Josef Jiricny -- Base Excision Repair / Lisiane B. Meira, Nicholas E. Burgis And Leona D. Samson -- Genomic Instability In Cancer Development / Penny A. Jeggo -- Translesion Synthesis And Error-prone Polymerases / Catherine M. Green And Alan R. Lehmann. Cell Cycle Progression And Chromosome Aberration -- The Ink4a/arf Network-cell Cycle Checkpoint Or Emergency Brake? / Ana Gutierrez Del Arroyo And Gordon Peters -- Dna Replication And Genomic Instability / Wenge Zhu, Tarek Abbas And Anindya Dutta -- The Dream Of Every Chromosome: Equal Segregation For A Healthy Life Of The Host / Tomohiro Matsumoto And Mitsuhiro Yanagida -- Telomere Structural Dynamics In Genome Integrity Control And Carcinogenesis / Roger A. Greenberg And K. Lenhard Rudolph -- Gene Amplification Mechanisms / Michelle Debatisse And Bernard Malfoy -- Dna Methylation And Cancer-associated Genetic Instability / Melanie Ehrlich. Deregulation Of The Centrosome Cycle And The Origin Of Chromosomal Instability In Cancer / Wilma L. Lingle, Kara Lukaswiewicz And Jeffrey L. Salisbury -- Genome Integrity Checkpoints -- Mammalian Dna Damage Response Pathway / Zhenkun Lou And Junjie Chen -- Atm And Cellular Response To Dna Damage / Martin F. Lavin ... [et Al.] -- Mitotic Checkpoint, Aneuploidy And Cancer / Tim J. Yen And Gary D. Kao. Edited By Erich A. Nigg. Includes Bibliographical References And Index. Cover 1 Frontmatter 3 Series Title Page 3 Title Page 4 Copyright 5 Table of Contents 6 Preface 8 List of Contributors 10 Part 1 - The Problem of Genome Instability 17 Chapter 1.1: THE MULTIPLICITY OF MUTATIONS IN HUMAN CANCERS 18 Chapter 1.2: MONITORING CHROMOSOME REARRANGEMENTS 33 Part 2 - DNA Repair and Mutagenesis 56 Chapter 2.1: NUCLEOTIDE EXCISION REPAIR AND ITS CONNECTION WITH CANCER AND AGEING 57 Chapter 2.2: DNA MISMATCH REPAIR AND COLON CANCER 96 Chapter 2.3: BASE EXCISION REPAIR 135 Chapter 2.4: GENOMIC INSTABILITY IN CANCER DEVELOPMENT 184 Chapter 2.5: TRANSLESION SYNTHESIS AND ERRORPRONE POLYMERASES 207 Part 3 - Cell Cycle Progression and Chromosome Aberration 232 Chapter 3.1: THE INK4A/ARF NETWORK – CELL CYCLE CHECKPOINT OR EMERGENCY BRAKE? 233 Chapter 3.2: DNA REPLICATION AND GENOMIC INSTABILITY 254 Chapter 3.3: THE DREAM OF EVERY CHROMOSOME: EQUAL SEGREGATION FOR A HEALTHY LIFE OF THE HOST 285 Chapter 3.4 TELOMERE STRUCTURAL DYNAMICS IN GENOME INTEGRITY CONTROL AND CARCINOGENESIS 315 Chapter 3.5: GENE AMPLIFICATION MECHANISMS 346 Chapter 3.6: DNA METHYLATION AND CANCER ASSOCIATEDGENETIC INSTABILITY 365 Chapter 3.7: DEREGULATION OF THE CENTROSOME CYCLE AND THE ORIGIN OF CHROMOSOMAL INSTABILITY IN CANCER 395 Part 4 - Genome Integrity Checkpoints 424 Chapter 4.1: MAMMALIAN DNA DAMAGE RESPONSE PATHWAY 425 Chapter 4.2: ATM AND CELLULAR RESPONSE TO DNA DAMAGE 456 Chapter 4.3: MITOTIC CHECKPOINT, ANEUPLOIDY AND CANCER 476 Index 499 The Multiplicity of Mutations in Human Cancers....Pages 3-17 Monitoring Chromosome Rearrangements....Pages 19-41 Nucleotide Excision Repair and its Connection with Cancer and Ageing....Pages 45-83 DNA Mismatch Repair and Colon Cancer....Pages 85-123 Base Excision Repair....Pages 125-173 Genomic Instability in Cancer Development....Pages 175-197 Translesion Synthesis And Errorprone Polymerases....Pages 199-223 The INK4A/Arf Network — Cell Cycle Checkpoint or Emergency Brake?....Pages 227-247 DNA Replication and Genomic Instability....Pages 249-279 The Dream of Every Chromosome: Equal Segregation for a Healthy Life of the Host....Pages 281-310 Telomere Structural Dynamics in Genome Integrity Control and Carcinogenesis....Pages 311-341 Gene Amplification Mechanisms....Pages 343-361 DNA Methylation and Cancer-associated Genetic Instability....Pages 363-392 Deregulation of the Centrosome Cycle and the Origin of Chromosomal Instability in Cancer....Pages 393-421 Mammalian DNA Damage Response Pathway....Pages 425-455 ATM and Cellular Response to DNA Damage....Pages 457-476 Mitotic Checkpoint, Aneuploidy and Cancer....Pages 477-499