Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells.

Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Abstract Text:

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

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.

Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Publishing Authors By Initials

SA McDonald,LC Greaves,L Gutierrez-Gonzalez,M Rodriguez-Justo,M Deheragoda,SJ Leedham,RW Taylor,CY Lee,SL Preston,M Lovell,T Hunt,G Elia,D Oukrif,R Harrison,MR Novelli,I Mitchell,DL Stoker,DM Turnbull,JA Jankowski,NA Wright,SA McDonald,LC Greaves,L Gutierrez-Gonzalez,M Rodriguez-Justo,M Deheragoda,SJ Leedham,RW Taylor,CY Lee,SL Preston,M Lovell,T Hunt,G Elia,D Oukrif,R Harrison,MR Novelli,I Mitchell,DL Stoker,DM Turnbull,JA Jankowski,NA Wright,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Gastroenterology

VOLUME: 134

Page Numbers: 500-10

Journal Abbreviation: Gastroenterology

ISSN: 1528-0012

DAY: 28

MONTH: 11

YEAR: 2007

Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 374630

Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells.

AFFILIATION: Histopathology Unit, London Research Institute, Cancer Research UK, London, United Kingdom. stuart.mcdonald@cancer.org.uk

Country: United States

AGENCY: United Kingdom Wellcome T

GRANT:

ACRONYM:

MEDLINETA: Gastroenterology

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells Related Publications

• A review of the epidemiologic aspects of embryo transfer from Brucella abortus -infected cows.
• Age and gender differences and predictors of victimization of the older homeless.
• Bovine amniotic and allantoic fluids for the culture of murine embryos.
• Bovine embryo morphology and evaluation.
• Coculture of bovine embryos with bovine fibroblasts.
• Cold culture of different stage mouse embryos in bicarbonated and bicarbonate-free media.
• Cold storage of mouse embryos of different stages of development.
• Deep freezing of mouse one-cell embryos and oocytes using different cryoprotectants.
• Determination of pentose phosphate and Embden-Meyerhof pathway activities in bovine embryos.
• Development of one-cell ovine embryos in two culture media under two gas atmospheres.
• Development of one-cell porcine embryos in two culture systems.
• Effect of one-step sucrose dilution of glycerol on in-vitro development of frozen-thawed mouse embyros.
• Expression of MUC2 epithelial mucin in breast carcinoma.
• Glucose utilization by enzymatically-formed trophoblastic vesicles and Day-14 porcine blastocysts.
• In vitro culture and maintenance of trophoblastic vesicles: Observations on the development of contractile structures with concurrent vessel development.
• Induction of estrus and superovulation in seasonally anestrous ewes.
• Non-surgical embryo transfer in cattle embryo-recipient interactions.
• Observations on the in vitro formation, development and differentiation of trilaminar vesicles formed from enzymatically dispersed porcine blastocysts.
• One-step sucrose dilution of frozen-thawed sheep embryos.
• Osteotomy for distal radius malunion.
• Pattern of sex steroids secretion and their relationship with embryo yield in Jersey cows superovulated with PMSG.
• Possible "immuno-protection" of the bovine parvovirus in the uterus: Preliminary communication.
• Quantity and quality of embryos collected from mice passively immunized against estradiol.
• Sucrose dilution of frozen mouse embryos: Interaction of glycerol and sucrose concentrations.
• Superovulation of cattle with equine pituitary extract and porcine ESH.
• Superovulation of progestagen synchronized ewes.
• Supervoulation of goats with FSH or FSH + LH following synchronization of estrus.
• The ability of fetal calf serum, new-born calf serum and normal steer serum to promote the in vitro development of bovine morulae.
• The effects of FSH-priming and dominant follicular regression on the superovulatory response of cattle.
• The use of tympanocentesis in the diagnosis and management of acute otitis media.