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Genomic Instability and Carcinogenesis: An Update
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 in...
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Formato: | Texto |
Lenguaje: | English |
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Bentham Science Publishers Ltd.
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694557/ https://www.ncbi.nlm.nih.gov/pubmed/19516960 http://dx.doi.org/10.2174/138920208786847926 |
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author | Abdel-Rahman, Wael M |
author_facet | Abdel-Rahman, Wael M |
author_sort | Abdel-Rahman, Wael M |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2694557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Bentham Science Publishers Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-26945572009-06-09 Genomic Instability and Carcinogenesis: An Update Abdel-Rahman, Wael M Curr Genomics Article 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. Bentham Science Publishers Ltd. 2008-12 /pmc/articles/PMC2694557/ /pubmed/19516960 http://dx.doi.org/10.2174/138920208786847926 Text en ©2008 Bentham Science Publishers Ltd. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/) which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Abdel-Rahman, Wael M Genomic Instability and Carcinogenesis: An Update |
title | Genomic Instability and Carcinogenesis: An Update |
title_full | Genomic Instability and Carcinogenesis: An Update |
title_fullStr | Genomic Instability and Carcinogenesis: An Update |
title_full_unstemmed | Genomic Instability and Carcinogenesis: An Update |
title_short | Genomic Instability and Carcinogenesis: An Update |
title_sort | genomic instability and carcinogenesis: an update |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694557/ https://www.ncbi.nlm.nih.gov/pubmed/19516960 http://dx.doi.org/10.2174/138920208786847926 |
work_keys_str_mv | AT abdelrahmanwaelm genomicinstabilityandcarcinogenesisanupdate |