Barrett Esophagus


The evolution of neoplastic cell lineages in Barrett esophagus is dominated by mutation, natural selection and genetic drift. The esophageal environment and therapies select for clones with competitive advantages that undergo selective sweeps, driving other cell types to extinction and providing a mechanism for expansion of neutral mutations as hitchhikers on the sweep.

Keywords: Barrett's; esophagus; cancer; evolution; selective sweep; genetic drift; hitchhiker; neoplastic progression

Figure 1.

There are multiple genetic routes to cancer in Barrett esophagus (BE). Each node in the diagram represents a cell population observed in our cohort. Clones were defined by loss of heterozygosity (LOH) assays. Nodes labeled 2N represent diploid cells that were ki67 positive, a nuclear antigen expressed by proliferating cells. Nodes labeled 4N represent biopsies with greater than 6% tetraploid cells. Nodes labeled aneuploid represent biopsies that included cells with abnormal complements of chromsomes, being neither diploid nor tetraploid. Each connection between two nodes represents an inferred ancestral relationship between two clones observed in the same individual. However, different branches in the diagram may have been observed in different individuals. The diagram is thus a summary, over the entire cohort, of the variety of different genetic routes to cancer. This stands in contrast to a strict linear ordering of genetic lesions in progression to cancer. (Reproduced with permission from Barrett et al., )



Barrett MT, Sanchez CA, Prevo LJ, et al. (1999) Evolution of neoplastic cell lineages in Barrett oesophagus. Nature Genetics 22: 106–109.

Cairns J (1975) Mutation selection and the natural history of cancer. Nature 255: 197–200.

Foultier MT, Vonarx‐Coinsman V, Xavier de Brito L, Robillard N and Patrice T (1994) DNA or cell kinetics flow cytometry analysis of 33 small gastrointestinal cancers treated by photodynamic therapy. Cancer 15: 1595–1607.

Galipeau PC, Prevo LJ, Sanchez CA, Longton GM and Reid BJ (1999) Clonal expansion and loss of heterozygosity at chromosomes 9p and 17p in premalignant esophageal (Barrett's) tissue. Journal of the National Cancer Institute 91: 2087–2095.

Goldie G and Coldman A (1984) The genetic origin of drug resistance in neoplasms: implications for systemic therapy. Cancer Research 44: 3643–3653.

Krishnadath KK, Wang KK, Taniguchi K, et al. (2000) Persistent genetic abnormalities in Barrett's esophagus after photodynamic therapy. Gastroenterology 119: 624–630.

Lagergren J, Bergstrom R, Lindgren A and Nyren O (1999) Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. New England Journal of Medicine 340: 825–831.

Prevo LJ, Sanchez CA, Galipeau PC and Reid BJ (1999) p53 mutant clones and field effects in Barrett's esophagus. Cancer Research 59: 4784–4787.

Sharma P, Morales TG, Bhattacharyya A, Garewal HS and Sampliner RE (1998) Squamous islands in Barrett's esophagus: what lies underneath? American Journal of Gastroenterology 93: 332–335.

Vaughan TL, Kristal AR, Blount PL, et al. (2002) NSAID use, BMI, and anthropometry in relation to genetic and cell cycle abnormalities in Barrett's esophagus. Cancer Epidemiology, Biomarkers and Prevention 11: 745–752.

Wong DJ, Paulson TG, Prevo LJ, et al. (2001) p16 INK4a lesions are common, early abnormalities that undergo clonal expansion in Barrett's metaplastic epithelium. Cancer Research 61: 8284–8289.

Further Reading

Booth C and Potten CS (2000) Gut instincts: thoughts on intestinal epithelial stem cells. Journal of Clinical Investigation 105: 1493–1499.

Garcia S, Park H, Novelli M and Wright N (1999) Field cancerization, clonality, and epithelial stem cells: the spread of mutated clones in epithelial sheets. Journal of Pathology 187: 61–81.

Hanahan D and Weinberg R (2000) The hallmarks of cancer. Cell 100: 57–70.

Heppner G and Miller F (1998) The cellular basis of tumor progression. International Review of Cytology 177: 1–56.

Hong MK, Laskin WB, Herman BE, et al. (1995) Expansion of the Ki‐67 proliferative compartment correlates with degree of dysplasia in Barrett's esophagus. Cancer 75: 423–429.

Kolar CS and Lodge DM (2001) Progress in invasion biology: predicting invaders. Trends in Ecology and Evolution 16: 199–204.

Naef AP, Savary M and Ozzello L (1975) Columnar‐lined lower esophagus, an acquired lesion with malignant predisposition: report on 140 cases of Barrett's esophagus with 12 adenocarcinomas. Journal of Thoracic and Cardiovascular Surgery 70: 826–835.

Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194: 23–28.

Nunney L (1999) Lineage selection and the evolution of multistage carcinogenesis. Proceedings of the Royal Society of London, Series B: Biological Sciences 266: 493–498.

Pannell JR and Charlesworth B (2000) Effects of metapopulation processes on measures of genetic diversity. Proceedings of the Royal Society of London, Series B: Biological Sciences 355: 1851–1864.

Rabinovitch PS, Longton G, Blount PL, Levine DS and Reid BJ (2001) Predictors of progression in Barrett's esophagus III: baseline flow cytometric variables. American Journal of Gastroenterology 96: 3071–3083.

Reid BJ, Prevo LJ, Galipeau PC, et al. (2001) Predictors of progression in Barrett's esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. American Journal of Gastroenterology 96: 2839–2848.

Web Links, peer‐reviewed information on Barrett esophagus, with references

Cyclin‐dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (CDKN2A); Locus ID: 1029. LocusLink:

Tumor protein p53 (Li–Fraumeni syndrome) (TP53); Locus ID: 7157. LocusLink:

Cyclin‐dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (CDKN2A); MIM number: 600160. OMIM:‐post/Omim/dispmim?600160

Tumor protein p53 (Li–Fraumeni syndrome) (TP53); MIM number: 191170. OMIM:‐post/Omim/dispmim?191170

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How to Cite close
Maley, Carlo C, and Reid, Brian J(Jan 2006) Barrett Esophagus. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0006068]