Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0546837 (esophageal cancer)
 8,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mutation and deletion of the multiple tumor suppressor genes, including p53, Rb, APC and MCC in the same tissue of humanesophageal cancer (EC) and adjacent non-tumor were analysed by PCR amplification and direct sequencing. In 10 cases of EC 6 were found mutations of p53 gene, 5 were found abnormality of Rb gene, 3 were found mutation of APC gene, 3 were found mutation of MCC gene, 8 were found atleration abnormality of tumor suppressor genes Rb, p53, APC and MCC, 6 were found two or more abnormality of the tumor suppressor genes. The results indicated that the alterations in multiple of tumor suppressor genes were related to carcinogenesis of human esophageal cancer.
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PMID:[The multiple tumor suppressor genes in human esophageal cancer]. 799 60

Squamous cell carcinoma of the esophagus has an uneven geographic distribution with a strong prevalence in the South Carolina Lowcountry. Although many environmental influences and some genetic factors have been implicated in its development, the molecular events required for tumorigenesis have not been defined. Point mutations in the p53 tumor suppressor gene are the most commonly noted genetic defect in human tumors. Our study shows that p53 point mutations occur more frequently in patients with esophageal cancer from this region than in patients from other areas of the world where the disease is prevalent.
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PMID:Prevalence of p53 mutations in patients with squamous cell carcinoma of the esophagus. 802 58

To understand whether p53 gene mutation is an early or late event in esophageal carcinogenesis, biopsy samples of esophageal epithelium from symptom-free subjects in a high incidence area, Huixian county of Henan Province, China, were analyzed. Mutations in exons 5, 6, 7, and 8 of p53 were analyzed by single-strand conformation polymorphism analysis and DNA sequencing. Among the 37 biopsy samples showing accumulation of p53 protein in immunohistochemical staining, missense mutations of p53 gene were detected in 1 of 3 samples with normal epithelia, 3 of 23 samples with basal cell hyperplasia, and 4 of 11 samples with dysplasia. All mutations occurred at exon 5 with 3 at codon 175, 2 at codon 176, and 1 each at codons 159, 135, and codon 132. Of the 8 mutations, there were 3 G to A transitions and 3 G to T transversions. To understand the mutation spectrum and possible causative factors of esophageal cancer in this area, surgically resected human primary esophageal carcinomas from Linxian county were analyzed for p53 gene mutations in exons 5, 6, 7, and 8. Mutations were detected in 16 of 29 samples (55%). Twelve samples contained different missense point mutations, with 75% transitions (7 G to A and 2 A to G) and 25% transversions (2 G to T and 1 G to C). Most of the mutations were located at either exon 5 or exon 7. A deletion and an insertion of nucleotides leading to frame-shift mutations were detected in each of two other samples. The results demonstrate that p53 protein accumulation and gene mutation may occur at very early stages of esophageal carcinogenesis. In carcinomas, there was a higher frequency of p53 gene mutations, which accounts for most of the cases with p53 protein accumulation.
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PMID:p53 tumor suppressor gene mutation in early esophageal precancerous lesions and carcinoma among high-risk populations in Henan, China. 804 81

A 45 base pair (bp) intragenic deletion of the p53 gene from a human esophageal cancer was analyzed in detail. This deletion contained all RNA splice consensus sequences at the 3' end of intron 7, including the RNA splice branch point, the pyrimidine-rich region and the 3' splice acceptor site. Northern blotting revealed a total lack of p53 mRNA expression in this tumor. Short direct repeats (TACTG) were found at the 5' and 3' breakpoints of the deletion and it removed one complete repeat as well as the entire region between the repeats. These results suggest that a 'slipped mispairing' mechanism occurring during DNA replication may generate p53 intragenic deletion in human esophageal cancer, leading to abolished p53 mRNA expression.
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PMID:A unique p53 intragenic deletion flanked by short direct repeats results in loss of mRNA expression in a human esophageal carcinoma. 805 46

To study the involvement of the p16 tumor suppressor gene in esophageal cancer development, we examined homozygous deletion of the p16 gene in 13 human esophageal cancer cell lines and 9 gastric cancer cell lines, in which some of genetic alterations have already been characterized. By Southern blot analysis, homozygous deletion was observed in 12 out of the 13 esophageal cancer cell lines (92%), in 2 out of a total of 9 gastric cancer cell lines (22%). It was also found that the p16 gene loss, cyclin D1 amplification and p53 gene mutations occurred independently in these cell lines. These findings suggest that loss or mutations of the p16 gene are involved in most esophageal cancers and that mutation of this gene plays a critical role in the development of esophageal cancer.
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PMID:Highly frequent homozygous deletion of the p16 gene in esophageal cancer cell lines. 809 26

In previous studies, we have shown that allelic loss on chromosome 17p, on which the p53 gene is located, is very frequent, and loss-of-function mutations of the p53 gene are closely associated with the tumorigenesis of esophageal cancer. In this study, we performed allelotype analysis to investigate whether other tumor suppressor genes are also involved in esophageal cancer. Using 55 polymorphic DNA markers covering every autosomal arm except 13p, 21p, and 22p, restriction fragment length polymorphism analysis was performed on 36 esophageal squamous cell carcinomas (ESCs) and their adjacent normal tissue samples. Frequent loss of heterozygosity (LOH) of > 30% of the informative cases was observed on chromosomes 3p (41.1%), 5q (52.6%), 6p (30.4%), 8p (33.3%), 9p (35.7%), 9q (30.8%), 11p (32.4%), 13q (52.7%), 17p (55.2%), 17q (33.3%), 18q (45.7%), and 19q (30.4%). Among these, LOH on 5q, 13q, 17p, and 18q was previously reported in ESC and is considered to involve the APC, RB, p53, and DCC genes, respectively. However, our deletion analysis of chromosome 18q revealed that the region commonly lost did not include the DCC locus, suggesting that a possible tumor suppressor gene on 18q other than the DCC gene is involved in ESC. We screened 60 primary ESC tumors and 20 cultured ESC cell lines for the mutation of the APC gene within a mutation cluster region in exon 15, where the "hot spot" of somatic mutation for colorectal and pancreatic cancers is thought to be. We could not find any mutation despite the high frequency of LOH on chromosome 5q. We also analyzed the relationship between the clinicopathological data and the allelic loss and found that LOH on chromosomes 6p and 13q was associated with poor prognosis.
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PMID:Allelotype analysis of esophageal squamous cell carcinoma. 818 88

The p53 tumor suppressor gene has been implicated in human esophageal tumorigenesis, and mutations are reported in primary esophageal adenocarcinomas and associated Barrett's epithelium. To evaluate the potential clinical significance of this molecular genetic marker in the progression of Barrett's epithelium to invasive esophageal cancer, we studied 20 patients with Barrett's epithelium, 10 of whom had an associated adenocarcinoma. p53 gene mutations were screened using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis and p53 oncoprotein distribution by immunohistochemistry. Point mutations were localized to exons 5 and 7 of the p53 gene, previously recognized as "hot spots." p53 gene mutations and immunoreactivity were detected in 7 of 10 patients with primary esophageal adenocarcinomas and in 6 patients with associated Barrett's epithelium, 3 of whom had high-grade dysplasia. Little correlation was observed between p53 positivity and clinicopathologic findings or outcome, although two patients with p53 mutations subsequently developed second primary cancers. Of 10 patients with Barrett's epithelium alone, 6 had p53 mutations, with mild or no dysplasia histologically, suggesting that p53 gene mutation may be an early event in progression to invasive cancer. No patient has developed invasive cancer to date, with a median follow-up of 8 years. These studies further implicate the p53 gene in the Barrett's epithelium-to-carcinoma sequence. Prospective surveillance studies incorporating molecular analysis of the p53 gene are warranted to further evaluate p53 as a predictor of patients at high risk for developing malignancy.
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PMID:Clinical implications of p53 gene mutation in the progression of Barrett's epithelium to invasive esophageal cancer. 831 Nov 40

The level of p53 protein was determined immunohistochemically in normal tissues and tissues with different severities of lesions (basal cell hyperplasia, dysplasia, carcinoma in situ, and carcinoma) from surgically resected human esophagi and esophageal biopsies of symptom-free subjects. The samples were from an area with high esophageal cancer incidence in northern China (Linxian and Huixian in the Henan province). Tissue sections were incubated with p53 antibodies for immunostaining. Conventional hematoxylin and eosin stain was also used. In surgically resected esophageal specimens, elevated p53 protein levels were found in the cell nuclei in tissues with precancerous and cancerous lesions. From basal cell hyperplasia to dysplasia to carcinoma in situ, the p53 immunostain-positive cells increased in number, and their distribution had roughly the same pattern as that of the proliferating cells. However, positive stain was not observed in the dividing basal cells of the normal epithelium of the surgically resected tissues. A similar pattern of immunostaining was observed in the abnormal tissues of the biopsy samples from the symptom-free subjects. An intriguing observation is that some p53 immunostain-positive cells were observed in 3 of 6 cases of histologically normal epithelia of biopsy samples. Only the papillary immunostaining pattern was observed in these three "normal" cases. Although the molecular basis for such positive stain remains to be investigated, it is possible that p53 protein accumulation occurs early in the pathogenesis of esophageal cancer and that p53 mutation is closely associated with the initiation of this cancer. The accumulation of p53 protein may be a promising early biomarker for identifying high-risk subjects for esophageal cancer.
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PMID:Accumulation of p53 protein in human esophageal precancerous lesions: a possible early biomarker for carcinogenesis. 846 96

Seventy-nine esophageal carcinoma patients were studied for genetic abnormalities in the p53 and Rb tumor suppressor genes. Single-strand conformation polymorphism analysis and DNA sequencing were used to detect p53 point mutations, Northern blotting was used to examine abnormal expression of p53 and Rb, and polymerase chain reaction and Southern blotting were used to analyze allelic loss. Twenty-five cases were analyzed by DNA sequencing to detect mutations in p53. Fourteen samples contained mutations within exons 5 through 9 of p53; seven had missense mutations giving rise to single amino acid substitutions. The remaining seven (50%) contained nonsense mutations leading to premature termination, five due to single base pair substitutions, and two that were the result of frameshift mutations. In other human tumors, p53 mutations are predominantly missense mutations, but our data as well as those from other groups show that nonsense mutations are common in human esophageal cancer. All but one of the constitutionally heterozygous samples containing mutations also manifested loss of the normal p53 allele; the one exception without allelic loss contained a silent mutation, which should not have had any affect on the p53 protein product. In addition, Northern blotting analysis revealed abnormalities (altered transcript size or mRNA levels) in 5 of 7 cases involving p53 and in 2 of 7 cases analyzed for Rb. Thirty-four cases were informative for allelic loss studies of both p53 and Rb; of these, 25 (74%) lost heterozygosity of p53, Rb, or both. When point mutations and mRNA expression abnormalities were also considered, 33 of 45 (73%) tumors informative for allelic loss assays of both genes as well as for mRNA or point mutation studies showed one or more abnormalities in p53 or Rb. Our results strongly suggest that a unique profile of molecular alterations involving p53 and Rb characterizes human esophageal cancer and that these specific genetic lesions are important in the development and/or progression of most human esophageal carcinomas.
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PMID:Altered messenger RNA and unique mutational profiles of p53 and Rb in human esophageal carcinomas. 846 10

More than 70 cell lines were established from esophageal cancer, including 15 TE-series cell lines established by the authors. This article reviews molecular and cellular features of esophageal cancer cells from studies using these cell lines as well as primary tumors. The subjects reviewed include primary cultures of normal epithelium of the esophagus and of esophageal tumors, their growth and differentiation properties, chromosomal aberrations, protein kinase C, growth factors and their receptors, oncogenes, and tumor-suppressor genes. Lesions of genetic loci in esophageal cancer include the absence of mutations in ras genes in primary tumors, amplification and overexpression of the c-erbB gene, co-amplification of hst-1 and int-2 genes, mutations, and allelic loss of tumor suppressor genes, p53, Rb, APC, and MCC. Future clinical improvement will be achieved on the basis of the understanding of molecular and cellular features of esophageal cancer cells.
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PMID:Molecular and cellular features of esophageal cancer cells. 850 34


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