Genomic instability and carcinogenesis: an update.

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.

journal_name

Curr Genomics

journal_title

Current genomics

authors

Abdel-Rahman WM

doi

10.2174/138920208786847926

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

535-41

issue

8

eissn

1389-2029

issn

1875-5488

journal_volume

9

pub_type

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