Genome Instability in Cancer Development

Ranga N. Venkatesan, Lawrence A. Loeb (auth.), Nathan Back, Irun R. Cohen, David Kritchevsky, Abel Lajtha, Rodolfo Paoletti, Erich A. Nigg (eds.)1402037635, 9781402037634, 1402037643, 9781402037641

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.

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Table of contents :
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