Recent investigations into Barrett's oesophagus at the level of individual crypts have found significant genetic heterogeneity within a single lesion. Furthermore, this genetic diversity has been shown to predict cancer development. In the present article, we review the genetic alterations implicated in disease progression in Barrett's oesophagus and discuss how genetic diversity could arise during tumorigenesis. Three arguments are discussed: a high mutation rate coupled with strong selection, clonal interaction driving progression, and a hitherto unidentified alteration that disrupts epithelial cell homoeostasis. Suggestions are made for future research to distinguish which of these theories is the predominant mechanism in Barrett's oesophagus-associated tumorigenesis.
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April 2010
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Conference Article|
March 22 2010
Genetic diversity during the development of Barrett's oesophagus-associated adenocarcinoma: how, when and why?
Trevor A. Graham;
Trevor A. Graham
1
*Histopathology Unit, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
1To whom correspondence should be addressed (email trevor.graham@cancer.org.uk).
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Stuart A.C. McDonald
Stuart A.C. McDonald
*Histopathology Unit, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
†Centre for Digestive Diseases, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London EC1 2AD, U.K.
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Publisher: Portland Press Ltd
Received:
October 30 2009
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem Soc Trans (2010) 38 (2): 374–379.
Article history
Received:
October 30 2009
Citation
Trevor A. Graham, Stuart A.C. McDonald; Genetic diversity during the development of Barrett's oesophagus-associated adenocarcinoma: how, when and why?. Biochem Soc Trans 1 April 2010; 38 (2): 374–379. doi: https://doi.org/10.1042/BST0380374
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