Field cancerization, clonality, and epithelial stem cells: the spread of mutated clones in epithelial sheets

Garcia, Sérgio Britto; Park, Hyun Sook; Novelli, Marco; Wright, Nicholas

doi:10.1002/(sici)1096-9896(199901)187:1<61::aid-path247>3.0.co;2-i

Cited by 150 publications

(91 citation statements)

References 213 publications

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“…A large body of evidence indicates that these parameters may be considered to be reliable premalignant lesions (6,9,14). Thus, our results support to the proposed assumption that colorectal carcinogenesis is at least partially prevented by colonic denervation.…”

Section: Discussionsupporting

confidence: 88%

“…In some cases the mutated clones, once established, spread through the tissues before becoming overtly invasive. There may be instances where such clones expand and remain cohesive, often involving a large tissue area, a phenomenon also called field cancerization (9). The present findings lead us to hypothesize that the action of neuropeptides could leave the denervated colonic mucosa less responsive to the action of chemical carcinogens and thus less favorable to the development of tumors.…”

Section: Discussionmentioning

confidence: 67%

“…It is possible that the smaller CFi may be related to the also smaller iBCC in G3 animals when compared to G2, since crypt fission has been proposed to explain the spread of mutated clones in the colonic mucosa (9).…”

Section: Discussionmentioning

confidence: 99%

“…The crypts themselves also reproduce by a process called crypt fission, beginning with a basal bifurcation and followed by a longitudinal division (9). It is thought that an increased rate of crypt fission, rather than hyperproliferation, is critical in precancerous gastrointestinal states (10).…”

Section: Introductionmentioning

confidence: 99%

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Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

Vespúcio

Turatti

Modiano

et al. 2008

Braz J Med Biol Res

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Denervation of the colon is protective against the colon cancer; however, the mechanisms involved are unknown. We tested the hypothesis that the denervated colonic mucosa could be less responsive to the action of the chemical carcinogen dimethylhydrazine (DMH). Three groups of 32 male Wistar rats were treated as follows: group 1 (G1) had the colon denervated with 0.3 mL 1.5 mM benzyldimethyltetradecylammonium (benzalkonium chloride, BAC); G2 received a single ip injection of 125 mg/kg DMH; G3 was treated with BAC + the same dose and route of DMH. A control group (Sham, N = 32) did not receive any treatment. Each group was subdivided into four groups according to the sacrifice time (1, 2, 6, and 12 weeks after DMH). Crypt fission index, ß-catenin accumulated crypts, aberrant crypt foci, and cell proliferation were evaluated and analyzed by ANOVA and the Student t-test. G3 animals presented a small number of aberrant crypt foci and low crypt fission index compared to G2 animals after 2 and 12 weeks, respectively. From the second week on, the index of ß-catenin crypt in G3 animals increased slower than in G2 animals. From the 12th week on, G2 animals presented a significant increase in cell proliferation when compared to the other groups. Colonic denervation plays an anticarcinogenic role from early stages of colon cancer development. This finding can be of importance for the study of the role of the enteric nervous system in the carcinogenic process.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

Vespúcio

Turatti

Modiano

et al. 2008

Braz J Med Biol Res

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“…An important aspect to be considered in clonal mutation is at what stage in the life-history of the tumor it is examined (17). It may progress from an early polyclonal reactive stage into a monoclonal expansion.…”

Section: Discussionmentioning

confidence: 99%

Clonality analysis of giant cell lesions of the jaws

et al. 2010

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Despite the importance of clonality to understand the pathogenesis and progression of tumors, it has not been investigated yet in giant cell lesions of the jaws. The aim of this study was to analyze the clonality of peripheral giant cell lesions (PGCL) and central giant cell lesions (CGCL) of the jaws. Six samples of PGCL and 5 samples of CGCL were analyzed in this study using the polymorphic human androgen receptor locus (HUMARA) assay. Three out of the 5 samples of the CGCL and 3 out of 6 samples of PGCL exhibited a monoclonal pattern. Our findings demonstrate that some giant cell lesions of the jaws are clonal, which indicate that these lesions may have a common genetic mechanism of development. Further studies are necessary to better elucidate the molecular mechanisms involved in the pathogenesis of such lesions.

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An Epigenetically Derived Monoclonal Origin for Recurrent Respiratory Papillomatosis

Stephen

Vaught

Chen

et al. 2007

Arch Otolaryngol Head Neck Surg

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To investigate the contribution of promoter methylation-mediated epigenetic events in recurrent respiratory papillomatosis tumorigenesis. Design: Archival tissue DNA, extracted from microdissected papilloma lesions, was interrogated for methylation status by means of the novel, multigene methylationspecific multiplex ligation-dependent probe amplification assay. Subjects: Fifteen subjects with recurrent respiratory papillomatosis, 3 females and 12 males, all with adult onset of illness (age range, 23-73 years) except for 1 female patient with juvenile onset (1 year old). Results: Promoter hypermethylation was recorded in 14 of 15 cases, and 19 of 22 unique methylation-prone can

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Field cancerization, clonality, and epithelial stem cells: the spread of mutated clones in epithelial sheets

Cited by 150 publications

References 213 publications

Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

Clonality analysis of giant cell lesions of the jaws

An Epigenetically Derived Monoclonal Origin for Recurrent Respiratory Papillomatosis

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