Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This conference concerned hereditary cancers of the breast, ovary, and colon, which are the common, often fatal, cancers with the greatest heritability in their causation. Four genes whose mutations impart dominantly heritable predisposition to one or more of these cancers have been cloned and one more has been mapped. The most molecular details are known for colon cancer. The APC gene of familial polyposis coli leads to the accumulation of numerous polyps, but the probability of transformation of the latter to cancer is low. This provides the opportunity to monitor putative preventive measures with an intermediate end point. In hereditary nonpolyposis colon cancer, transformation of the polyp to cancer is accelerated by an inherited mutation in either of two DNA mismatch repair genes. The discovery of an intermediate end point could be very helpful for breast cancer. Testing persons at risk for predisposing mutations depends heavily on the availability of promising measures for prevention or treatment.
 ...
PMID:Hereditary cancers: from discovery to intervention. 857 54

A human colon carcinoma cell line designated OUMS-23 has been established from metastatic pericardial fluid of a male familial adenomatous polyposis patient with colon cancer. Since 1984, the epithelial cells have been maintained in culture. Ultrastructural studies revealed the presence of numerous microvilli on the cell surface and desmosomes between the adjacent cells. The cells secreted carcinoembryonic antigen into the culture medium (15 ng/10(6) cells-1 24 h-1). The cells expressed heat-stable placental-type-like alkaline phosphatase, whereas the normal counterparts expressed tissue-unspecific alkaline phosphatase. Karyotypic analysis showed that the cell line was of human origin and that the chromosome number was broadly distributed between 53 and 118. Southern blot analysis of the APC gene revealed no abnormalities in OUMS-24 cells, while Northern blot analysis demonstrated that the expression of the gene was about one-half that of the normal human fibroblasts. No mutations at the "hot spots" of codons 12 and 61 of H-, K- and N-ras proto-oncogenes were detected in the cells. The cells could grow in soft agar at a cloning efficiency of 6.5%, and upon transplantation into nude mice the cells formed tumors, which were diagnosed as differentiated adenocarcinoma.
 ...
PMID:Establishment and characterization of a human colon cancer cell line, OUMS-23, from a patient with familial adenomatous polyposis. 857 85

The predisposition to colon cancer is multigenetically controlled in animals and probably also in humans. We have analyzed the multigenic control of susceptibility to 1,2-dimethylhydrazine-induced colon tumors in mice by using a set of 20 homozygous CcS/Dem recombinant congenic strains, each of which contains a different random subset of approximately 12.5% of genes from the susceptible strain STS/A and 87.5% of genes from the relatively resistant strain BALB/cHeA. Some CcS/Dem strains received the alleles from the susceptible strain STS/A at one or more of the multiple colon tumor susceptibility loci and are susceptible, whereas others are resistant. Linkage analysis shows that these susceptibility genes are different from the mouse homologs of the genes known to be somatically mutated in human colon cancer (KRAS2, TP53, DCC, MCC, APC, MSH2, and probably also MLH1). Different subsets of genes control tumor numbers and size. Two colon cancer susceptibility genes, Scc1 and Scc2, map to mouse chromosome 2. The Scc1 locus has been mapped to a narrow region of 2.4 centimorgans (90% confidence interval).
 ...
PMID:Fine mapping of colon tumor susceptibility (Scc) genes in the mouse, different from the genes known to be somatically mutated in colon cancer. 857 18

A database is described in which over 700 mutations in the human APC gene of tumors (colon cancer predominantly) are compiled from the literature. It includes both molecular informations about the mutations and also clinical data about the patients. A software have been designed in order to analyse all these informations in the database.
 ...
PMID:APC gene: database of germline and somatic mutations in human tumors and cell lines. 859 58

Plakoglobin is a major component of the submembranal plaque of adherens junctions and desmosomes in mammalian cells. It is closely related to the Drosophila segment polarity gene armadillo which has a role in the transduction of transmembrane signals that regulate cell fate. Like its close homologue beta-catenin, plakoglobin can associate with the product of the tumor suppressor gene APC that is linked to human colon cancer. We have studied the effect of plakoglobin overexpression, and the cooperation between plakoglobin and N-cadherin, on the morphology and tumorigenic ability of cells either lacking, or expressing cadherin and alpha- and beta-catenin. Overexpression of plakoglobin in SV40-transformed 3T3 (SVT2) cells suppressed the tumorigenicity of the cells in syngeneic mice. Transfection with N-cadherin conferred an epithelial phenotype on the cell culture, but had no significant effect on the tumorigenicity of the cells. Cotransfection of plakoglobin and N-cadherin into SVT2 cells, however, was considerably more effective in tumor suppression than plakoglobin overexpression alone. Finally, transfection of plakoglobin into a human renal carcinoma cell line that expresses neither cadherins nor plakoglobin, or alpha-and beta-catenin, resulted in a dose-dependent suppression of tumor formation by these cells in nude mice. Plakoglobin, in these cells, did not exhibit junctional localization and was diffusely distributed in the cytoplasm, with a significant amount of the protein also localized in the nucleus. The results suggest that plakoglobin can efficiently suppress the tumorigenicity of cells in the presence of, or independently of the cadherin-catenin complex.
 ...
PMID:Suppression of tumorigenicity by plakoglobin: an augmenting effect of N-cadherin. 860 8

Mutation of the APC gene may be a common denominator of all human colon cancer--polypoid and non-polypoid familial cancer as well as sporadic occurrences. Fearon and Vogelstein (1990) have described a series of molecular changes during the progression of human colon cancer, beginning with mutations in APC. Min is a strain of the laboratory mouse carrying a nonsense mutation in Apc, the mouse homologue of APC. The Min strain has been used to test the effect of germline alterations in certain genes identified in the progression pathway of Fearon and Vogelstein. A deficiency in DNA cytosine methylase leads to a reduction in the tumour multiplicity of Min mice contrary to the a priori expectation based on the global hypomethylation of the DNA of early colonic neoplasms. Alterations in Kras had no perceptible effect on the tumour multiplicity of Min mice but may not have been successfully directed to the proliferative cell population. Constitutional mutation of p53 did not influence the multiplicity or histopathology of early Min induced intestinal tumours. The cause and effect analysis of the genetics of colon cancer is clearly in an early phase. An unlinked genetic factor interacting with Min in controlling intestinal tumour multiplicity is Mom1. A central goal for the near future is to identify the Mom1 gene product and to identify other loci that can interact with the Min mutation and affect tumour multiplicity or progression. Mouse chimaeras will permit an analysis of the clonality and cell autonomy of Min induced neoplasms and also of the action of Mom1. The results of these analyses will inform investigators as to what modes of prevention and therapy might be designed for particular tumour types. The Min strain thereby presents an opportunity to discover protective factors against human colon cancer.
 ...
PMID:Emergent issues in the genetics of intestinal neoplasia. 871 26

The genetic understanding of colon cancer susceptibility is advancing very rapidly; it has already had a major impact on clinical management, and we have only seen the beginning. Genes responsible for the two well-defined familial colon cancer syndromes (APC and HNPCC) have been identified. These syndromes can now often be diagnosed by genetic rather than by endoscopic screening of the at-risk individuals in a family. Linkage analysis, although clinically cumbersome, can be performed for families with both APC and HNPCC. In some families, the mutation itself can be determined and a specific mutation assay can be used in the other at-risk members of the family. Both linkage analysis and mutational assays are still largely performed in specialized high-risk cancer clinics. For APC, a truncated protein assay performed on cells isolated from peripheral blood is now commercially available, so the genetic diagnosis of APC can be made by any clinician. It is important, however, to be able to provide appropriate genetic counseling to families before and after genetic testing for these familial colon cancer syndromes. The familial clustering of "sporadic" colon cancer has been suggested to be due to the inheritance of a susceptibility gene or genes. A family history of colon cancer has become an important stratification criteria for colon cancer screening programs. Colonoscopic screening is indicated for individuals with two or more FDRs with colon cancer or with one FDR in whom colon cancer developed under the age of 50 or so. If specific susceptibility genes for sporadic colon cancer are identified, it will be possible to target powerful primary preventive and screening programs to this high-risk population (susceptibility gene carriers).
 ...
PMID:The genetic basis of colorectal cancer risk. 890 98

Mutations in the APC gene are responsible for the dominantly inherited colon cancer syndrome, familial adenomatous polyposis (FAP). We have designed PCR primers which allow amplification by RT-PCR of exons 1-14 of the APC gene in six overlapping segments. The amplicons have been screened for the presence of mutations in patients affected with FAP using heteroduplex analysis. One patient has been identified with an alternatively spliced transcript involving exon 14 and a single base insertion mutation within the same exon.
 ...
PMID:Mutation detection in exons 1-14 of the adenomatous polyposis coli gene: identification of an alternatively spliced transcript. 891 Aug 93

Aberrant crypt foci (ACF) are distinct microscopic lesions of the colon thought to be the earliest identifiable precursors of colon cancer. As precursors of colon cancer, ACF may contain mutations in genes that are altered early in colorectal tumorigenesis. Candidates for these genes include APC, K-Ras, and those of the DNA mismatch repair system. Some colon cancers with mutations in DNA mismatch repair genes are characterized by genomic instability at simple repeated sequences, also known as microsatellite instability. In this study, we analyzed 19 ACF (> or = 20 crypts/focus) and adjoining, microscopically normal colonic mucosa from 10 colon cancer patients for the presence of microsatellite instability. DNA from two ACF from two different patients displayed microsatellite instability. None of the DNA samples from normal mucosa displayed microsatellite instability. These observations support the role of ACF as a precursor to colon cancer and provide some evidence that mutations in DNA mismatch repair genes are early somatic events in colon cancer.
 ...
PMID:Microsatellite instability in aberrant crypt foci from human colons. 896 80

Germline mutations of the APC (adenomatous polyposis coli) gene lead to multiple intestinal tumors in familial adenomatous polyposis patients and in Min (multiple intestinal neoplasia) mice. Consequently, these mice provide an excellent model for familial colon cancer. We have identified an Mr approx. 66 kDa glycoprotein which is preferentially expressed at the cell surface of cell lines established from chemically induced rat colon carcinomas. Cloning of the corresponding Tage4 cDNA has revealed that this protein contains the conserved amino acids characteristic of members of the immunoglobulin gene superfamily. Here, we analyze expression of the mouse Tage4 gene in Min mouse intestinal adenomas. RT-PCR analysis allowed us to detect expression of this gene in all the mouse adenomas tested. In contrast, lower levels of Tage4 mRNA were found in the intestinal tract and barely detectable levels in other tissues of normal mice. Furthermore, Tage4 mRNA was detected in a series of mouse intestinal adenomas by in situ hybridization. A strong signal was seen in the samples analyzed.
 ...
PMID:Over-expression of a novel member of the immunoglobulin superfamily in Min mouse intestinal adenomas. 898 Jan 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>