Abstract
Barrett’s esophagus (BO) is a preneoplastic condition described as the replacement of the stratified squamous epithelium of the distal esophagus with one that histologically presents as a diverse mixture of metaplastic glands resembling gastric or intestinal-type columnar epithelium. The clonal origins of BO are still unclear. More recently, we have begun to investigate the relationship between the various metaplastic gland phenotypes observed in BO, how they evolve, and the cancer risk they bestow. Studies have revealed that glands along the BO segment are clonal units containing a single stem cell clone that can give rise to all the differentiated epithelial cell types in glands. Clonal lineage tracing analysis has revealed that Barrett’s glands are capable of bifurcation and this facilitates clonal expansion and competition. In fact, BO in some patients appears to consist of multiple, independently initiated clones that compete with each other for space and possibly resources. This chapter discusses the concepts of clonal competition and expansion in BO and sets out to query what we know about the role of gland diversity and phenotypic evolution within this complex columnar metaplasia.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Fitzgerald RC, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014;63(1):7–42.
Zeki S, Fitzgerald RC. Targeting care in Barrett’s oesophagus. Clin Med. 2014;14 Suppl 6:s78–83.
Hvid-Jensen F, et al. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med. 2011;365(15):1375–83.
Hardie LJ, et al. p16 expression in Barrett’s esophagus and esophageal adenocarcinoma: association with genetic and epigenetic alterations. Cancer Lett. 2005;217(2):221–30.
Wong DJ, et al. p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett’s metaplastic epithelium. Cancer Res. 2001;61(22):8284–9.
Galipeau PC, et al. Clonal expansion and loss of heterozygosity at chromosomes 9p and 17p in premalignant esophageal (Barrett’s) tissue. J Natl Cancer Inst. 1999;91(24):2087–95.
Li X, et al. Temporal and spatial evolution of somatic chromosomal alterations: a case-cohort study of Barrett’s esophagus. Cancer Prev Res (Phila). 2014;7(1):114–27.
Ross-Innes CS, et al. Whole-genome sequencing provides new insights into the clonal architecture of Barrett’s esophagus and esophageal adenocarcinoma. Nat Genet. 2015;47(9):1038–46.
Weaver JM, et al. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet. 2014;46(8):837–43.
Stachler MD, et al. Paired exome analysis of Barrett’s esophagus and adenocarcinoma. Nat Genet. 2015;47(9):1047–55.
McDonald SA, et al. Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol. 2015;12(1):50–60.
Barbera M, et al. The human squamous oesophagus has widespread capacity for clonal expansion from cells at diverse stages of differentiation. Gut. 2015;64(1):11–9.
Lavery DL, et al. The stem cell organisation, and the proliferative and gene expression profile of Barrett’s epithelium, replicates pyloric-type gastric glands. Gut. 2014;63(12):1854–63.
Baker AM, et al. Characterization of LGR5 stem cells in colorectal adenomas and carcinomas. Sci Rep. 2015;5:8654.
Pan Q, et al. Identification of lineage-uncommitted, long-lived, label-retaining cells in healthy human esophagus and stomach, and in metaplastic esophagus. Gastroenterology. 2013;144(4):761–70.
Hahn HP, et al. Intestinal differentiation in metaplastic, nongoblet columnar epithelium in the esophagus. Am J Surg Pathol. 2009;33(7):1006–15.
Gottfried MR, McClave SA, Boyce HW. Incomplete intestinal metaplasia in the diagnosis of columnar lined esophagus (Barrett’s esophagus). Am J Clin Pathol. 1989;92(6):741–6.
Thompson JJ, Zinsser KR, Enterline HT. Barrett’s metaplasia and adenocarcinoma of the esophagus and gastroesophageal junction. Hum Pathol. 1983;14(1):42–61.
Going JJ, et al. Zoning of mucosal phenotype, dysplasia, and telomerase activity measured by telomerase repeat assay protocol in Barrett’s esophagus. Neoplasia. 2004;6(1):85–92.
Wang X, et al. Residual embryonic cells as precursors of a Barrett’s-like metaplasia. Cell. 2011;145(7):1023–35.
Yen TH, Wright NA. The gastrointestinal tract stem cell niche. Stem Cell Rev. 2006;2(3):203–12.
Leedham SJ, et al. Gastrointestinal stem cells and cancer: bridging the molecular gap. Stem Cell Rev. 2005;1(3):233–41.
Zeki SS, Graham TA, Wright NA. Stem cells and their implications for colorectal cancer. Nat Rev Gastroenterol Hepatol. 2011;8(2):90–100.
Kozar S, et al. Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas. Cell Stem Cell. 2013;13(5):626–33.
Lopez-Garcia C, et al. Intestinal stem cell replacement follows a pattern of neutral drift. Science. 2010;330(6005):822–5.
Novelli M, et al. X-inactivation patch size in human female tissue confounds the assessment of tumor clonality. Proc Natl Acad Sci U S A. 2003;100(6):3311–4.
Salk JJ, et al. Clonal expansions in ulcerative colitis identify patients with neoplasia. Proc Natl Acad Sci U S A. 2009;106(49):20871–6.
Maegawa S, et al. Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res. 2010;20(3):332–40.
Humphries A, et al. Lineage tracing reveals multipotent stem cells maintain human adenomas and the pattern of clonal expansion in tumor evolution. Proc Natl Acad Sci U S A. 2013;110(27):E2490–9.
Taylor RW, et al. Mitochondrial DNA mutations in human colonic crypt stem cells. J Clin Invest. 2003;112(9):1351–60.
McDonald SA, et al. Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Gastroenterology. 2008;134(2):500–10.
Nicholson AM, et al. Barrett’s metaplasia glands are clonal, contain multiple stem cells and share a common squamous progenitor. Gut. 2012;61(10):1380–9.
Baker AM, et al. Quantification of crypt and stem cell evolution in the normal and neoplastic human colon. Cell Rep. 2014;8(4):940–7.
Cheng H, et al. Crypt production in normal and diseased human colonic epithelium. Anat Rec. 1986;216(1):44–8.
Gatenby PA, et al. Does the length of the columnar-lined esophagus change with time? Dis Esophagus. 2007;20(6):497–503.
Moawad FJ, et al. Barrett’s oesophagus length is established at the time of initial endoscopy and does not change over time: results from a large multicentre cohort. Gut. 2015;64(12):1874–80.
Nowell PC. The clonal evolution of tumor cell populations. Science. 1976;194(4260):23–8.
Barrett MT, et al. Evolution of neoplastic cell lineages in Barrett oesophagus. Nat Genet. 1999;22(1):106–9.
Leedham SJ, et al. Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett’s oesophagus. Gut. 2008;57(8):1041–8.
Maley CC, et al. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet. 2006;38(4):468–73.
Jones S, et al. Comparative lesion sequencing provides insights into tumor evolution. Proc Natl Acad Sci U S A. 2008;105(11):4283–8.
Lavery DL. et al. Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett’s oesophagus. Gut. 2016;65:907–13.
Zeki SS, et al. Clonal selection and persistence in dysplastic Barrett’s esophagus and intramucosal cancers after failed radiofrequency ablation. Am J Gastroenterol. 2013;108(10):1584–92.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Evans, J.A., McDonald, S.A.C. (2016). The Complex, Clonal, and Controversial Nature of Barrett’s Esophagus. In: Jansen, M., Wright, N. (eds) Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract. Advances in Experimental Medicine and Biology, vol 908. Springer, Cham. https://doi.org/10.1007/978-3-319-41388-4_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-41388-4_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-41386-0
Online ISBN: 978-3-319-41388-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)