Genetic pathways involved in the progression of Barrett's metaplasia to adenocarcinoma.
BACKGROUND
The prediction of which patients with Barrett's metaplasia will develop cancer is difficult. Better genetic characterization of the condition may aid clinicians in devising more effective management and follow-up strategies.


METHODS
A review was undertaken of the accumulated genetic data relating to the progression of squamous epithelium to adenocarcinoma. The normal functions of a number of cancer-related genes are described and an explanation is given of how alterations in these genes interfere with normal cell processes and lead to cancer.


CONCLUSIONS
The main genetic alterations accompanying the progression through dysplasia to adenocarcinoma were collated from 135 papers. The principal genetic changes implicated are the loss of p16 gene expression (by deletion or hypermethylation), the loss of p53 expression (by mutation and deletion), the increase in cyclin D1 expression, the induction of aneuploidy and the losses of the Rb, DCC and APC chromosomal loci.
Jenkins
G J S
GJ
Human Molecular Pathology Group, Swansea Clinical School, University of Wales Swansea, UK. g.j.jenkins@swansea.ac.uk
Doak
S H
SH
Parry
J M
JM
D'Souza
F R
FR
Griffiths
A P
AP
Baxter
J N
JN
D000230:Adenocarcinoma / Q000235:genetics*; D001471:Barrett Esophagus / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D009154:Mutation / Q000235:genetics; D009857:Oncogenes / Q000235:genetics