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Inherited and inducible chromosomal instability: a fragile bridge between genome integrity mechanisms and tumourigenesis
Author(s) -
Wright Eric G.
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199901)187:1<19::aid-path233>3.0.co;2-1
Subject(s) - chromosome instability , genome instability , bloom syndrome , biology , genetics , phenotype , ataxia telangiectasia , mutation , carcinogenesis , cancer research , chromosome , gene , dna damage , dna , helicase , rna
Cancer is a multi‐step process evolving as the result of the accumulation of a number of mutational events. The growing body of evidence implicating genetic instability as a key feature of this evolutionary process and the risk of malignancy associated with chromosomal instability syndromes highlight the importance of understanding the mechanisms that cells use to maintain the integrity of their genomes. Classic examples of inherited chromosomal instability with cancer predisposition are Bloom's syndrome, ataxia telangiectasia, and Fanconi anaemia, although the mechanisms involved are far from understood. Selected features of these inherited disorders are reviewed to provide a background to the more recently discovered inducible chromosomal instability, a phenotype in which apparently normal cells that have survived ionizing radiation and certain chemical insults may produce descendants exhibiting a high frequency of de novo chromosome aberrations and gene mutations. The phenotype is induced at frequencies considerably greater than conventional mutation frequencies but little is understood of the underlying mechanism(s). To date, chromosomal instability induced by ionizing radiation has been the most extensively studied phenotype and it is evident that the expression of inducible instability has a strong dependence on the type of radiation exposure, the cell type irradiated, and the genetic ‘predisposition’ of the irradiated cell. Copyright © 1999 John Wiley & Sons, Ltd.