Genetic Instability and Tumorigenesis

M. B. KASTAN Cancer is a disease resulting from alterations of cellular genes which cause phe notypic changes in somatic cells. Usually, when we think about genetic diseases, we think about inheriting one or two abnormal genes from our parents and these gene abnormalities confer the disease phenotype. In contrast, in the majority of cancers, no such inherited gene abnormalities can be identified (which does not mean that they do not exist) and there is no obvious family history suggesting an inherited disease. The vast majority of genes which are altered in the cancer cells are not transmitted through the germ line, but rather become abnormal in somatic cells sometime during the lifetime of the individual. Thus, the critical question which arises is "how do these genetic changes occur in somatic cells?". Epidemiologic data suggest that exposure to environmental carcinogens con tributes to the genesis of at least 80% of all human cancers (DOLL and PETO 1981). Thus, it is natural to suspect that the genetic changes in somatic cells which con tribute to the transformed phenotype arise from DNA damage caused by such exposures. Therefore, understanding how cells respond to DNA-damaging agents is likely to be an important component of our understanding of the genesis of human tumors.

Klappentext

This book reviews our current level of understanding of the role of genetic instability in human tumorigenesis. In this most rapidly moving field, discoveries in recent years have elucidated a number of important gene products which control cellular responses to DNA damaging agents, e.g., DNA repair and cell cycle perturbations. Mutations in these genes appear to be important contributors to the development of a significant percentage of human tumors. The reviews cover the gamut from scientific insights into genetic instability learned from simple model systems, e.g., yeast, to the genes which control these processes in human cells and contribute to human tumor development. Such information is being used to develop approaches to reduce cancer development and to provide more specific targets to improve cancer therapies.

Inhalt
List of Contents.- Genetic Instability and Tumorigenesis: Introduction.- Genomic Stability and Instability: A Working Paradigm.- Surveillance and Genome Stability in Budding Yeast: Implications for Mammalian Carcinogenesis.- Genomic Instability and Its Role in Neoplasia.- Role of DNA Excision Repair Gene Defects in the Etiology of Cancer.- Chromosome Instability Syndromes: Lessons for Carcinogenesis.- Genetic Alterations in Human Tumors.