Analysis of the premalignant stages of Barrett's oesophagus through to adenocarcinoma by comparative genomic hybridization.
OBJECTIVE
Barrett's oesophagus is a pre-neoplastic lesion, which develops as a complication of chronic gastro-oesophageal reflux disease and predisposes the patient to oesophageal adenocarcinoma. Our aim was to characterize karyotypic changes that may occur during the progression of Barrett's metaplasia through low-grade dysplasia and high-grade dysplasia to adenocarcinoma.


METHODS
The technique of comparative genomic hybridization was used to characterize genome-wide changes in biopsies from patients with low-grade dysplasia, low-grade dysplasia plus high-grade dysplasia, high-grade dysplasia or adenocarcinoma. Both fresh and archival material was examined.


RESULTS
Comparative genomic hybridization revealed a large amount of widespread chromosome instability at the high-grade dysplasia stage. No significant chromosome changes were detectable by comparative genomic hybridization in patients with low-grade dysplasia. Karyotypic changes in the adenocarcinoma patients were more specific than those found in the high-grade dysplasia patients. Chromosome 4 was amplified most often in high-grade dysplasia and chromosome 8q was amplified most frequently in the adenocarcinomas.


CONCLUSIONS
These data demonstrate that high-grade dysplasia is the stage exhibiting widespread chromosome instability, which is detectable by comparative genomic hybridization. This instability is undetectable in low-grade dysplasia. The chromosome variation seen at high-grade dysplasia may be the source of more specific karyotypes that progress to adenocarcinoma. Importantly, we have identified chromosome 4 amplification as being heavily involved in the initiation of Barrett's progression. Specific chromosome changes (4 and 8q) may represent important regions on which to focus attention in future studies, with a view to identifying diagnostic markers.
Croft
Jeanette
J
Human Molecular Pathology Group, Swansea Clinical School, University of Wales, UK.
Parry
Elizabeth M
EM
Jenkins
Gareth J
GJ
Doak
Shareen H
SH
Baxter
John N
JN
Griffiths
A Paul
AP
Brown
Tim H
TH
Parry
James M
JM
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D009367:Neoplasm Staging; D021141:Nucleic Acid Amplification Techniques; D009693:Nucleic Acid Hybridization / Q000379:methods; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*