Genetic pathways involved in the progression of Barrett's metaplasia to adenocarcinoma

Jenkins, Gareth; Doak, Shareen H.; Parry, James M.; D'Souza, Francis R.; Griffiths, Ann; Baxter, J. N.

doi:10.1046/j.1365-2168.2002.02107.x

Cited by 105 publications

(102 citation statements)

References 94 publications

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“…Like in breast carcinoma, mutations of the p53 gene appear to play an important role in the development of oesophageal squamous cell carcinoma, dysplastic Barrett's epithelium and the progression to oesophageal adenocarcinoma (Casson et al, 1991;Neshat et al, 1994;Wu et al, 1998). Ample studies have reported mutations in p53 in oesophageal carcinomas, with mutation frequencies varying from 40 to 90% (Jankowski et al, 1999;Mandard et al, 2000;Wijnhoven et al, 2001;Jenkins et al, 2002). As CHEK2 and p53 are thought to be participants of the same biological pathway, we aimed to establish whether CHEK2*1100delC confers susceptibility to oesophageal cancer, by determining the frequency of the mutation among an unselected series of oesophageal cancers and precursor lesions.…”

mentioning

confidence: 99%

The CHEK2*1100delC mutation has no major contribution in oesophageal carcinogenesis

Koppert

Schutte

Abbou³

et al. 2004

Br J Cancer

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In response to DNA damage, the cell cycle checkpoint kinase 2 (CHEK2) may phosphorylate p53, Cdc25A and Cdc25C, and regulate BRCA1 function, leading to cell cycle arrest and DNA repair. The truncating germline mutation CHEK2*1100delC abrogates kinase activity and confers low-penetrance susceptibility to breast cancer. We found CHEK2*1100delC in 0.5% of 190 oesophageal squamous cell carcinomas and in 1.5% of 196 oesophageal adenocarcinomas. In addition, we observed the mutation in 3.0% of 99 Barrett's metaplasias and 1.5% of 66 dysplastic Barrett's epithelia, both known precursor lesions of oesophageal adenocarcinoma. Since CHEK2*1100delC mutation frequencies did not significantly differ among oesophageal squamous cell carcinomas, adenocarcinomas and (dysplastic) Barrett's epithelia, as compared to healthy individuals, we conclude that the CHEK2*1100delC mutation has no major contribution in oesophageal carcinogenesis.

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mentioning

confidence: 99%

The CHEK2*1100delC mutation has no major contribution in oesophageal carcinogenesis

Koppert

Schutte

Abbou³

et al. 2004

Br J Cancer

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“…Despite advances in treatment of EAC, its prognosis is still poor (Falk, 2002). The molecular basis of the development of EAC, although extensively studied (Jenkins et al, 2002;Brabender et al, 2004;McManus et al, 2004;Metzger et al, 2004), is not completely understood. Better understanding of the molecular alterations during its development might improve prevention and tumor control and ultimately lead to better disease management.…”

Section: Introductionmentioning

confidence: 99%

Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus

et al. 2006

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Aberrant activation of the Wnt signaling pathway has been reported during neoplastic progression in Barrett's esophagus (BE). However, mutations in APC and CTNNB1 genes were rarely observed. In this study, expression pattern of Wnt ligands, Frizzled receptors and APC, as well as the methylation status of the APC, SFRP1 and SFRP2 promoter genes were investigated in normal esophageal mucosa and in preneoplastic and neoplastic lesions of BE patients. Promoter methylation of APC was found in all BE samples and in 95% of esophageal adenocarcinomas (EAC). Full methylation of APC correlated with lack of expression. In EAC, nuclear translocation of b-catenin was observed regardless of the expression of APC. WNT2 expression was higher in dysplasia and EAC than in BE, with 20/26 (77%) of the EAC showing high expression of WNT2. SFRP1 methylation occurred in all BE samples and in 96% of EAC, while SFRP2 was methylated in 73% of the normal squamous esophageal mucosa samples. In conclusion, (1) alterations of key regulators of the Wnt signaling are frequent in the pathogenesis of BE; (2) the APC and SFRP1 genes are inactivated by promoter methylation in BE; (3) the WNT2 gene is upregulated along the progression from low-grade dysplasia to EAC.

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“…The genes involved in the development of Barrett's metaplasia seem to be: p16, APC, Rb, p53, DCC which are lost in this early step. Moreover, cyclin D1 could be amplified, p53 mutated, APC hypermethylated and Bcl2, iNOS, COX-2, CDX2, SRC, SKI, SnoN overexpressed (9)(10)(11).…”

Section: From Metaplasia To Adenocarcinomamentioning

confidence: 99%

“…Aneuploidy has been detected in ADC, dysplastic tissue and metaplastic Barrett's epithelium (13) but others authors suggested that aneuploidy characterizes more the dysplastic and the tumor development then the metaplastic step (14). Cell signalling genes such as HER-2 (also called ERBB2, HER-2/neu, NEU), EGFR, TGFa gene, Kras seems to be overexpressed/amplified in adenocarcinomas arisen in BE but not in metaplasia, appearing to be a late event (9,15). Conversely, TFF1, MUC5AC, meprin A and sucrose isomaltase are always positive in non dysplastic BE and negative in dysplasia (16).…”

Section: From Metaplasia To Adenocarcinomamentioning

confidence: 99%

“…Presumably, not a single gene might be able to discriminate those patients that will progress to high grade dysplasia (HGD)/adenocarcinoma (ADC). Some investigations (9) show that the selection of markers based on DNA array experiments may provide molecular criteria for discrimination of pathologic conditions of esophageal epithelium and that the expression analysis of a limited number of highly selected genes may have clinical usefulness for the treatment of patients with this disease. The genes involved in the development of Barrett's metaplasia seem to be: p16, APC, Rb, p53, DCC which are lost in this early step.…”

Section: From Metaplasia To Adenocarcinomamentioning

confidence: 99%

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Influence of genetics on tumoral pathologies: The example of the adenocarcinoma arising in Barrett's esophagus

Villanacci

Bassotti

Salemme

et al. 2012

Rev. esp. enferm. dig.

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Barrett's esophagus (BE) refers to an abnormal change (metaplasia) in the cells of the inferior portion of the esophagus. About 10% of patients with symptomatic gastroesophageal reflux disease (GERD) have BE. In some cases, BE develops as an advanced stage of erosive esophagitis. The risk of esophageal cancer appears to be increased in patients with BE. The only way to diagnose BE is by endoscopy and histology. Some studies suggest that intensive treatment of Barrett's esophagus with effective acid suppression can reduce the amount of abnormal lining in the esophagus. It is not clear whether such treatment also prevents esophageal cancer. Generally, the cancer starts out as carcinoma of the esophagus on the surface, and then invades the surrounding tissue. Surgery offers the best chance of long-term survival. There are many events that occur in Barrett's esophagus that lead to the development of cancer and most of them appear to occur early, before high-grade dysplasia or cancer develops. No one knows what the late events are and how cells acquire the ability to leave their normal growth boundaries. It is now widely accepted that the development of most cancers is due to something called genomic or genetic instability. The aim of this review is to show BE pathology in its progression to cancer looking for new biomarkers to distinguish between BE -dysplasia (low grade and high grade)-adenocarcinoma (ADC) and to characterize the ADC, giving more hope for its treatment.

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Genetic pathways involved in the progression of Barrett's metaplasia to adenocarcinoma

Cited by 105 publications

References 94 publications

The CHEK2*1100delC mutation has no major contribution in oesophageal carcinogenesis

The CHEK2*1100delC mutation has no major contribution in oesophageal carcinogenesis

Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus

Influence of genetics on tumoral pathologies: The example of the adenocarcinoma arising in Barrett's esophagus

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