Abstract
Cancers arise as a result of stepwise accumulation of mutations which may occur at the nucleotide level and/or the gross chromosomal level. Many cancers particularly those of the colon display a form of genomic instability which may facilitate and speed up tumor initiation and development. In few instances, a “mutator mutation” has been clearly implicated in driving the accumulation of other carcinogenic mutations. For example, the post-replicative DNA mismatch repair deficiency results in dramatic increase in insertion/deletion mutations giving rise to the microsatellite instability (MSI) phenotype and may predispose to a spectrum of tumours when it occurs in the germline. Although many sporadic cancers show multiple mutations suggesting unstable genome, the role of this instability in carcinogenesis, as opposed to the power of natural selection, has been a matter of controversy. This review gives an update of the latest data on these issues particularly recent data from genome-wide, high throughput techniques as well as mathematical modelling. Throughout this review, reference will be made to the relevance of genomic instability to the pathogenesis of colorectal carcinoma particularly its hereditary and familial subsets.
Keywords: Genomic instability, Genetic instability, chromosomal instability, microsatellite instability, colorectal cancer, Lynch syndrome, HNPCC, familial colorectal cancer type-X, mismatch repair
Current Genomics
Title: Genomic Instability and Carcinogenesis: An Update
Volume: 9 Issue: 8
Author(s): Wael M. Abdel-Rahman
Affiliation:
Keywords: Genomic instability, Genetic instability, chromosomal instability, microsatellite instability, colorectal cancer, Lynch syndrome, HNPCC, familial colorectal cancer type-X, mismatch repair
Abstract: Cancers arise as a result of stepwise accumulation of mutations which may occur at the nucleotide level and/or the gross chromosomal level. Many cancers particularly those of the colon display a form of genomic instability which may facilitate and speed up tumor initiation and development. In few instances, a “mutator mutation” has been clearly implicated in driving the accumulation of other carcinogenic mutations. For example, the post-replicative DNA mismatch repair deficiency results in dramatic increase in insertion/deletion mutations giving rise to the microsatellite instability (MSI) phenotype and may predispose to a spectrum of tumours when it occurs in the germline. Although many sporadic cancers show multiple mutations suggesting unstable genome, the role of this instability in carcinogenesis, as opposed to the power of natural selection, has been a matter of controversy. This review gives an update of the latest data on these issues particularly recent data from genome-wide, high throughput techniques as well as mathematical modelling. Throughout this review, reference will be made to the relevance of genomic instability to the pathogenesis of colorectal carcinoma particularly its hereditary and familial subsets.
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Cite this article as:
Abdel-Rahman M. Wael, Genomic Instability and Carcinogenesis: An Update, Current Genomics 2008; 9 (8) . https://dx.doi.org/10.2174/138920208786847926
DOI https://dx.doi.org/10.2174/138920208786847926 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
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