Genome Instability in Cancer Development

ISBN-13: 9781402037634 / Angielski / Twarda / 2005 / 512 str.

Erucg A. Nigg; Erich A. Nigg

Opis

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.

Spis treści

Part 1. The Problem of Genome Instability 1.1. The Multiplicity of Mutations in Human Cancers by Ranga N. Venkatesan and Lawrence A. Loeb 1.2. Monitoring chromosome rearrangements by Michael R. Speicher Part 2. DNA Repair and Mutagenesis 2.1. Nucleotide excision repair and its connection with cancer and ageing by Jaan-Olle Andressoo, Jan H.J. Hoeijmakers and Harm de Waard 2.2. DNA mismatch repair and colon cancer by Giancarlo Marra and Josef Jiricny 2.3. Base excision repair by Lisiane B. Meira, Nicholas E. Burgis and Leona D. Samson 2.4. DNA double strand break repair by Penny A. Jeggo 2.5. Translesion synthesis and error-prone polymerases by Catherine M. Green and Alan R. Lehmann Part 3. Cell Cycle Progression and Chromosome Aberrations 3.1. The INK4A/ARF network - cell cycle checkpoint or emergency brake? By Ana Gutierrez del Arroyo and Gordon Peters 3.2. DNA replication and genomic instability by Wenge Zhu, Tarek Abbas and Anindya Dutta 3.3. The dream of every chromosome: equal segregation for a healthy life of the host by Tomohiro Matsumoto and Mitsuhiro Yanagida 3.4. Telomere structural dynamics in genome integrity control and carcinogenesis by Roger A. Greenberg and K. Lenhard Rudolph 3.5. Gene amplification mechanisms by Michelle Debatisse and Bernard Malfoy 3.6. DNA methylation and cancer-associated genetic instability by Melanie Ehrlich 3.7. Deregulation of the centrosome cycle and the origin of chromosomal instability in cancer by Wilma L. Lingle, Kara Lukaswiewicz and Jeffrey L. Salisbury Part 4. Genome Integrity Checkpoints 4.1. Mammalian DNA damage response pathway by Zhenkun Lou and Junjie Chen 4.2. ATM and cellular response to DNA damage by Martin F Lavin, Sergei Kozlov, Nuri Gueven, Cheng Peng, Geoff Birrell, Phillip Chen and Shaun Scott 4.3 Kinetochore function, chromosome segregation and the spindle assembly checkpoint by Tim J. Yen and Gary D. Kao