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Cited by 242Gastric Cancer Management and OutcomesCancer Cells and MetastasisCancer Genomics and Diagnostics

The DOI matches its Crossref record; 28 of the 30 references it cites were found in a registry or an index.

Mechanisms of Field Cancerization in the Human Stomach: The Expansion and Spread of Mutated Gastric Stem Cells

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McDonald, Stuart A.C., Greaves, Laura C., Gutierrez–Gonzalez, Lydia, Rodriguez–Justo, Manuel, Deheragoda, Maesha, Leedham, Simon J., Taylor, Robert W., Lee, Chung Yin, Preston, Sean L., Lovell, Matthew, Hunt, Toby, Elia, George, Oukrif, Dahmane, Harrison, Rebecca, Novelli, Marco R., Mitchell, Ian, Stoker, David L., Turnbull, Douglass M., Jankowski, Janusz A.Z., Wright, Nicholas A.·2008·Gastroenterology
DOI 10.1053/j.gastro.2007.11.035
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Abstract

Background & aims How mutations are established and spread through the human stomach is unclear because the clonal structure of gastric mucosal units is unknown. Here we investigate, using mitochondrial DNA (mtDNA) mutations as a marker of clonal expansion, the clonality of the gastric unit and show how mutations expand in normal mucosa and gastric mucosa showing intestinal metaplasia. This has important implications in gastric carcinogenesis.Methods Mutated units were identified by a histochemical method to detect activity of cytochrome c oxidase. Negative units were laser-capture microdissected, and mutations were identified by polymerase chain reaction sequencing. Differentiated epithelial cells were identified by immunohistochemistry for lineage markers.Results We show that mtDNA mutations establish themselves in stem cells within normal human gastric body units, and are passed on to all their differentiated progeny, thereby providing evidence for clonal conversion to a new stem cell-derived unit-monoclonal conversion, encompassing all gastric epithelial lineages. The presence of partially mutated units indicates that more than one stem cell is present in each unit. Mutated units can divide by fission to form patches, with each unit sharing an indentical, mutant mtDNA genotype. Furthermore, we show that intestinal metaplastic crypts are clonal, possess multiple stem cells, and that fission is a mechanism by which intestinal metaplasia spreads.Conclusions These data show that human gastric body units are clonal, contain multiple multipotential stem cells, and provide definitive evidence for how mutations spread within the human stomach, and show how field cancerization develops.

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Crossref · 10.1053/j.gastro.2007.11.035

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  1. Park, 1995, Crypt fission in the small intestine and colon, Am J Pathol, 147, 1416

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Metadata

Authors
McDonald, S. A. C., Greaves, L. C., Gutierrez–Gonzalez, L., Rodriguez–Justo, M., Deheragoda, M., Leedham, S. J., Taylor, R. W., Lee, C. Y., Preston, S. L., Lovell, M., Hunt, T., Elia, G., Oukrif, D., Harrison, R., Novelli, M. R., Mitchell, I., Stoker, D. L., Turnbull, D. M., Jankowski, J. A. Z., & Wright, N. A.
Affiliations
  • Cancer Research UK (GB)
  • Newcastle University (GB)
  • University College London (GB)
  • University Hospitals of Leicester NHS Trust (GB)
  • University College Hospital (GB)
  • University of London (GB)
Corresponding author
McDonald, Stuart A.C.
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2008-02
Volume
134
Issue
2
Pages
500-510
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2007.11.035
OpenAlex
W2096969440
Cited by
242
References
30
Citations by year
2026: 5 · 2025: 8 · 2024: 3 · 2023: 9 · 2022: 9 · 2021: 11 · 2020: 13 · 2019: 6 · 2018: 13 · 2017: 18 · 2016: 17 · 2015: 14 · 2014: 16 · 2013: 16 · 2012: 14
FWCI
13.98
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • CLOK (University of Central Lancashire) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • Wellcome Trust
  • Cancer Research UK
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Oncology › Gastric Cancer Management and Outcomes
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
field cancerization, gastric stem cells, clonal expansion, mitochondrial DNA mutations, cytochrome c oxidase, intestinal metaplasia, gastric carcinogenesis, gastric mucosa, multipotent stem cells
MeSH terms
Cell Transformation, Neoplastic, Electron Transport Complex IV, DNA, Mitochondrial, Epithelium, Gastric Mucosa, Genotype, Humans, Metaplasia, Mutation, Precancerous Conditions, Stomach, Stomach Neoplasms, Multipotent Stem Cells

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