The Difference in p53 Mutations between Cancers of the Upper and Lower Gastrointestinal Tract

Oki, Eiji; Zhao, Yan; Yoshida, Rika; Egashira, Akinori; Ohgaki, Kippei; Morita, Masaru; Kakeji, Yoshihiro; Maehara, Yoshihiko

doi:10.1159/000167864

Cited by 39 publications

(32 citation statements)

References 57 publications

(29 reference statements)

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“…The major adduct of BaP produces a G-to-T transversion [52], and 40%-50% of p53 gene mutations in Japanese patients with ESCC are predominantly the transversion of G to T [70,71]; these findings also suggest that cigarette smoke might be related to esophageal carcinogenesis. However, Pfeifer et al [35] have noted that it is difficult to identify the unambiguous molecular signature of tobacco carcinogens in the p53 mutational spectrum of esophageal cancer, because the patterns of mutation are extremely heterogeneous.…”

Section: General Mechanisms Of Smoking-induced Carcinogenesismentioning

confidence: 99%

Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: molecular mechanisms of carcinogenesis

et al. 2010

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Esophageal cancer is the eighth most common incident cancer in the world and ranks sixth among all cancers in mortality. Esophageal cancers are classified into two histological types; esophageal squamous cell carcinoma (ESCC), and adenocarcinoma, and the incidences of these types show a striking variety of geographic distribution, possibly reflecting differences in exposure to specific environmental factors. Both alcohol consumption and cigarette smoking are major risk factors for the development of ESCC. Acetaldehyde is the most toxic ethanol metabolite in alcohol-associated carcinogenesis, while ethanol itself stimulates carcinogenesis by inhibiting DNA methylation and by interacting with retinoid metabolism. Cigarette smoke contains more than 60 carcinogens and there are strong links between some of these carcinogens and various smoking-induced cancers; these mechanisms are well established. Synergistic effects of cigarette smoking and alcohol consumption are also observed in carcinogenesis of the upper aerodigestive tract. Of note, intensive molecular biological studies have revealed the molecular mechanisms involved in the development of ESCC, including genetic and epigenetic alterations. However, a wide range of molecular changes is associated with ESCC, possibly because the esophagus is exposed to many kinds of carcinogens including alcohol and cigarette smoke, and it remains unclear which alterations are the most critical for esophageal carcinogenesis. This brief review summarizes the general mechanisms of alcohol- and smoking-induced carcinogenesis and then discusses the mechanisms of the development of ESCC, with special attention to alcohol consumption and cigarette smoking.

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Section: General Mechanisms Of Smoking-induced Carcinogenesismentioning

confidence: 99%

Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: molecular mechanisms of carcinogenesis

et al. 2010

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“…DNA was extracted as described previously (23,24). Briefly, the frozen samples were incubated in a lysis buffer (0.01 mol/L Tris-HCl, pH 8.0; 0.1 mol/L EDTA, pH 8.0; 0.5% SDS) containing proteinase K (100 mg/mL) at 37 C for 2 hours.…”

Section: Dna Preparationmentioning

confidence: 99%

“…PCR direct sequencing of the p53 gene As previously described (23,24), using with genomic DNA extracted from cell lines and tissue samples, a 275-bp fragment containing exon 6, a 439-bp fragment containing exon 7, and a 445-bp fragment containing exons 8 and 9 of the p53 gene were amplified by PCR (Nippon Gene). The PCR primers for the amplification of a 406-bp fragment containing exon 5 of p53 were as follows: exon 5 forward, TGC AGG AGG TGC TTA CAC ATG; exon 5 reverse, TCC ACT CGG ATA AGA TGC TG.…”

Section: Dna Preparationmentioning

confidence: 99%

Copy-Neutral Loss of Heterozygosity at the p53 Locus in Carcinogenesis of Esophageal Squamous Cell Carcinomas Associated with p53 Mutations

Saeki¹,

Kitao²,

Yoshinaga³

et al. 2011

Clinical Cancer Research

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Purpose: LOH at the p53 locus has been reported to be associated with esophageal squamous cell carcinogenesis. The aim of this study is to identify potential mechanisms resulting in LOH around the p53 locus in its carcinogenesis.Experimental Design: We investigated 10 esophageal cancer cell lines and 91 surgically resected specimens, examining them for LOH at the p53 locus on chromosome 17. We examined the p53 gene by using microsatellite analysis, comparative genomic hybridization (CGH), FISH, and single-nucleotide polymorphism-CGH (SNP-CGH).Results: In an analysis of specimens by microsatellite markers, a close positive correlation was found between p53 mutations and LOH at the p53 locus (P < 0.01). Although four cell lines were found to be homozygous for p53 mutations, LOH at the p53 locus was not detected by CGH. Among two p53 mutant cancer cell lines and five p53 mutant/LOH cancer specimens analyzed by FISH, both the cell lines and four of the specimens exhibited no obvious copy number loss at the p53 locus. SNP-CGH analysis, which allows both determination of DNA copy number and detection of copy-neutral LOH, showed that LOHs without copy number change were caused by whole or large chromosomal alteration.Conclusions: LOH without copy number change at the p53 locus was observed in p53 mutant esophageal squamous cell carcinomas. Our data suggest that copy-neutral LOH occurring as a result of chromosomal instability might be the major mechanism for inactivation of the intact allele in esophageal squamous cell carcinogenesis associated with p53 mutation.

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“…A high frequency of TP53 mutations and p53 protein expression in ESCC has been reported [5,6], and both have been assessed as potential predictive markers of chemotherapy response and prognosis for ESCC [7][8][9][10]. However, the association between p53 expression and clinicopathological findings or prognosis remains controversial.…”

Section: Introductionmentioning

confidence: 99%

p53 is an independent prognostic factor in operable esophageal squamous cell carcinoma: a large-scale study with a long follow-up

Zheng

Tao

et al. 2014

Med Oncol

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The p53 protein is involved in many biological functions in cancer, such as cell cycle arrest, DNA repair, apoptosis, senescence, DNA metabolism, angiogenesis, and cellular differentiation. However, the association between p53 expression and clinicopathological findings or prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. We designed a large-scale study of 830 operable ESCC patients with a long follow-up to investigate the relationship between p53 expression and the clinicopathological characteristics and prognosis of patients. Immunohistochemistry was used to detect p53 protein expression. When the patients were divided into two groups, a positive expression group and a negative expression group, p53-positive expression positively correlated with a poorer differentiation level (P = 0.044). The overexpression of p53 was associated with a more advanced clinical stage (P = 0.015). A total of 775 patients were available for survival analysis. The median OS of 160 patients who had p53-positive expression and 486 patients who had p53-negative expression were 58.8 and 46.3 months, respectively (P = 0.021); the median PFS of the two groups were 39.6 and 27.5 months, respectively (P = 0.015). Lymph node metastasis, gender, differentiation, depth of invasion, and p53 protein expression were proven to have an influence on both OS and PFS in a univariate analysis. In the multivariate analysis, p53-positive expression maintained its independent prognostic impact on OS (P = 0.048) and PFS (P = 0.039), as did lymph node metastasis, differentiation, and depth of invasion. We identified that p53 protein-positive expression can serve as an independent, unfavorable prognosis biomarker in ESCC.

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The Difference in p53 Mutations between Cancers of the Upper and Lower Gastrointestinal Tract

Cited by 39 publications

References 57 publications

Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: molecular mechanisms of carcinogenesis

Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: molecular mechanisms of carcinogenesis

Copy-Neutral Loss of Heterozygosity at the p53 Locus in Carcinogenesis of Esophageal Squamous Cell Carcinomas Associated with p53 Mutations

p53 is an independent prognostic factor in operable esophageal squamous cell carcinoma: a large-scale study with a long follow-up

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