Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have suggested that abnormalities in the adenomatous polyposis coli gene (APC gene) are associated with the development not only of familial adenomatous polyposis coli (FAP) but also of cancers in digestive organs. In order to elucidate whether abnormalities of the APC gene could contribute to the development of oral squamous-cell carcinoma (SCC), genomic DNAs from tumors and normal tissues of 24 unrelated Japanese patients were examined by using PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) and sequence analyses. Five novel nucleotide substitutions of the APC gene in tumor tissues were identified in 3 patients with oral SCC (12.5%), resulting in 3 amino-acid replacements or a truncation of the APC gene product. We also examined 24 tumor and 24 normal tissue samples for loss of heterozygosity (LOH) at exon 11 of the APC gene by PCR-LOH assay. In this analysis, 45.8% of samples were informative and LOH was detected in 72.7% of informative cases. The frequency of LOH in oral SCC was similar to that previously reported in esophageal SCC. These results suggest that abnormalities in the APC gene are associated with the development of human oral SCC.
Int J Cancer 1994 Sep 15
PMID:Abnormalities of the adenomatous polyposis coli gene in human oral squamous-cell carcinoma. 792 73

APC (adenomatous polyposis coli) protein is differentially expressed in the normal colonic crypt and believed to be involved in colonic cell maturation. In this work we investigated whether expression of the APC protein is associated with cell death in colonic epithelial cells. We have previously reported an in vitro system to study apoptosis. Briefly, cells attached to the flask have a low frequency of apoptosis (1-3%), whereas cells that detach from the flask and float in the medium have a high proportion of apoptotic cells (36-96% depending on the cell line). The full-length 300-kDa or truncated APC protein, normally expressed by the attached cells (detected using the FE9 antibody), was found to be lost in the floating apoptotic cells in 8/11 colon tumour cell lines examined. In addition, the APC antibody FE9 detected a 90-kDa protein in the floating apoptotic cells of all cell lines investigated, which was not present in attached cells. Furthermore, loss of full-length APC and gain of the 90-kDa protein was observed in the apoptotic cells of 2 cell lines derived from other tissues: the SV40-transformed fibroblast cell line CMSV40fib and the lymphoblastoid B-cell line BJA-B. In cells repeatedly frozen and thawed, believed to induce necrotic cell death, full-length or truncated APC was also lost, though a 95-kDa protein distinct from that in apoptotic cells was observed. Specific loss of full-length or truncated APC (resulting in a 90-kDa protein in apoptotic cells but a 95-kDa protein in necrotic cells) is therefore associated with cell death. Our findings suggest a possible role for APC in cell survival.
Int J Cancer 1994 Oct 01
PMID:Loss of APC protein expressed by human colonic epithelial cells and the appearance of a specific low-molecular-weight form is associated with apoptosis in vitro. 792 5

The aim was to determine whether proton magnetic resonance spectroscopy (MRS) could grade human colorectal cells of differing malignant potential. A cell model of tumour development and progression comprising 2 non-tumorigenic adenoma lines and 4 carcinoma lines of increasing tumorigenicity was chosen. A gradual reduction in cellular differentiation and an accumulation of genetic alterations from adenoma to carcinoma characterized the selected cell lines. One-dimensional and 2-dimensional MRS showed that reduced differentiation in the cell model correlated with an increase in the levels of lipid, metabolites, the glycosylation intermediate uridine diphospho-N-acetylglucosamine and cell-surface fucosylation. Mutations involving the K-ras, APC and DCC genes are present both in adenoma- and in carcinoma-derived lines in this model, but the first evidence of an abnormality in the p53 gene was concomitant with the cells' ability to grow as a tumour in athymic nude mice. This genetic change coincided with the detection, by MRS, of UDP-hexose (ribose moiety, 2D MRS cross peak between H2 at 4.38 ppm and HI at 5.99 ppm) and the appearance of an additional fucosyl resonance (cross peak between-CH3 at 1.41 and H5 at 4.30 ppm) in the least tumorigenic of the carcinoma cell lines. An increase in complexity of the fucosylation spectral pattern was observed with further cellular de-differentiation and increased tumorigenicity. Collectively these data support the existence of an adenoma-carcinoma sequence.
Int J Cancer 1994 Oct 15
PMID:Correlation of cellular differentiation in human colorectal carcinoma and adenoma cell lines with metabolite profiles determined by 1H magnetic resonance spectroscopy. 792 26

Papillary thyroid carcinoma (PTC) is one of several tumours associated with familial adenomatous polyposis (FAP), an inherited tumour syndrome which appears to result from germ-line mutation of the APC tumour suppressor gene. Here we investigate the possibility that somatic mutation of APC might play a role in sporadic PTC. 16 cases of PTC together with matched normal tissue were examined by single-strand conformation polymorphism (SSCP) analysis, concentrating on the mutation cluster region (MCR) of the APC gene (codons 1286-1513). No evidence of mutation was observed in any sample. We conclude that APC mutation, at least in the MCR, is not a significant causal mechanism in sporadic PTC.
Eur J Cancer 1994
PMID:Evidence against involvement of APC mutation in papillary thyroid carcinoma. 794 97

We report here the use of multiplex fluorescent polymerase chain reaction (PCR) for quantitative allele loss detection using microsatellites with 2-5 base pair repeat motifs. Allele loss of APC, DCC, p53 and RB1 in colorectal tumours has been reported previously using a variety of methods. However, not all workers used intragenic markers. We have used microsatellite polymorphisms which map within, or are closely linked to, these tumour-suppressor gene loci in order to determine whether these loci are indeed the targets for alteration in colorectal cancer. In addition, we have assayed two other tumour-suppressor genes, WT1 and NF1, to see whether they play a role in colorectal carcinogenesis. The putative metastasis-suppressor gene, NM23, was also investigated since there have been conflicting reports about its involvement in colorectal carcinogenesis. Allele loss was detected at the DCC (29%), p53 (66%), RB1 (50%) and NF1 (14%) loci and in the APC/MCC region (50%), but not at the WT1 or NM23 loci. These rapid, and mostly gene-specific, fluorescent multiplex PCR assays for allele loss detection could be modified to devise a single molecular diagnostic test for the important lesions in colorectal cancer.
Br J Cancer 1994 Nov
PMID:Frequency of allele loss of DCC, p53, RBI, WT1, NF1, NM23 and APC/MCC in colorectal cancer assayed by fluorescent multiplex polymerase chain reaction. 794 85

Familial adenomatous polyposis is a rare genetic disease with a dominant mode of inheritance, involved in 1% of colorectal cancer. The APC gene, responsible for the disease, has been localized on the long arm of chromosome 5 and has recently been cloned and sequenced. Mutations predicted to alter the coding property of the APC gene have been reported in large series of adenomatous polyposis patients. Some of them have been correlated with an attenuated phenotype. A genetic test has been developed in affected families. Systematic screening of registered at-risk relatives has allowed a significant reduction of the median age at adenomatous polyposis diagnosis, and thus the incidence of colorectal cancer.
Bull Cancer 1994 Jan
PMID:[Familial adenomatous polyposis]. 794 87

Hereditary predisposition to colorectal cancer assumes two well-defined forms: familial adenomatous polyposis and hereditary nonpolyposis colon cancer. These tumors segregate as autosomal dominant conditions whose penetrance increases with age; cancer is expected to develop ultimately in as much as 50% of the offspring of affected individuals. These traits account for less than 1% and approximately 5% of all colorectal cancer, respectively. In addition, first-degree relatives of patients with common (sporadic) colorectal neoplasia are at increased risk of colorectal cancer. This relative risk averages approximately twofold but is significantly higher for relatives of younger patients (age at diagnosis, < 55 years). Familial adenomatous polyposis and a major subset of hereditary nonpolyposis colon cancer are due to loss-of-function germline mutations of genes located on chromosomes 5q and 2p, respectively. Both of these genes have been cloned recently. The gene affected in familial polyposis, APC, encodes a protein of unknown function that normally is found on the surface of maturing cells in the upper colonic crypts. The relevant gene in many hereditary nonpolyposis colon cancer kindreds is hMSH2. This gene encodes the human homologue of a bacterial protein MutS, which is part of a system known to repair base mismatches in newly replicated DNA. Loss of hMSH2 function may explain the strikingly erroneous replication of short DNA repeats (microsatellites) in colon tumors from patients with hereditary nonpolyposis colon cancer. Because this error-prone replication is found in approximately 13% of nonfamilial colon cancers, defective mismatch repair may contribute to the development of both hereditary and sporadic colon neoplasia. Molecular genetic assays to detect mutated alleles of these genes will facilitate presymptomatic identification of carriers in families with familial polyposis and hereditary nonpolyposis colon cancer. Current recommendations for surveillance of family members are presented in the light of the new genetic understanding of these diseases.
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PMID:Southwestern internal medicine conference: hereditary predisposition to colorectal cancer: new insights. 797 49

Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour-suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma.
Br J Cancer 1994 Dec
PMID:Analysis of adenomatous polyposis coli gene in thyroid tumours. 798 Oct 58

Our study was undertaken to determine the prognostic significance of several common genetic alterations observed in colorectal carcinomas. We have previously analysed loss of heterozygosity of the MCC, APC, p53 and DCC tumour suppressor gene loci as well as p53 gene mutations and protein over-expression in a series of 100 Dukes' stage B and C colorectal tumours obtained at surgery. To extend our observations of alterations that may occur in these tumours, mutations to the c-Ki-ras oncogene and APC tumour suppressor gene were detected by PCR single-strand conformation polymorphism analysis. Short-term follow-up revealed no significant association between overall patient survival and any single, or combination of, genetic alteration(s). Surprisingly, patients whose tumours showed evidence of p53 protein over-expression/accumulation by immunocytochemistry (ICC) had a significantly better prognosis (p = 0.039) than those whose tumours had no p53 ICC reactivity.
Int J Cancer 1994 Dec 15
PMID:The common molecular genetic alterations in Dukes' B and C colorectal carcinomas are not short-term prognostic indicators of survival. 798 12

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


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