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)

Generalized genomic instability, detected as somatic changes in allele sizes at microsatellite loci in tumors compared to peripheral lymphocyte DNA, is a recently recognized mechanism of mutation in cancer. Such instability results from the somatic loss of DNA mismatch repair capability. Germ-line mutations at DNA mismatch repair loci confer susceptibility to colon cancer in hereditary non-polyposis colorectal cancer. Somatic loss of DNA mismatch repair has been reported in a large variety of other tumor types. Our goal was to determine the frequency of microsatellite instability in a large series of oral tumors. Out of 91 tumors analyzed for microsatellite instability, 6 (7%) showed microsatellite instability. Instability was observed at multiple loci with a range of 50-74% of loci affected. Alterations include both increase (74%) and decrease (26%) in allele sizes. The proportion of alleles affected ranged from 30-58% of all alleles. Our data suggest that somatic genomic instability plays a role in the pathogenesis of a small subset of oral tumors.
 ...
PMID:Microsatellite instability in oral cancer. 759 6

Genetic instability has been recently related to point mutations on genes involved in DNA repair pathway of errors produced during replication. These molecular alterations have been described in hereditary and sporadic colon carcinomas and related tumors. To examine genetic instability on lympho- and myeloproliferative processes, we analyzed the behaviour of 10 microsatellite markers and one VNTR on different chromosomes in 10 patients with non-Hodgkin lymphomas (NHL), one patient with acute lymphoblastic leukemia (ALL) and 10 patients with acute myeloid leukemia (AML). Mobility shifts were found in three of those cases. One of them showed genetic instability for several markers--microsatellites and VNTR- and the other two showed differences for only one marker. As a correlation between point mutations in MSH2 gene and the presence of genetic instability in hereditary non-polyposis colon cancer (HNPCC) and related tumors has been found, we analyzed the sequence of a conversed region of this gene in the cases showing this phenomenon. We only found a polymorphism, previously described, in 669 codon from cDNA.
 ...
PMID:Genetic instability of microsatellites in hematological neoplasms. 759 85

Hereditary Non-polyposis Colon Cancer Syndrome (HNPCC) is the most common cause of familial colorectal cancer. Molecular genetic studies of HNPCC have shown evidence of locus heterogeneity, and mutations in four genes (hMSH2, hMLH1, hPMS1, and hPMS2) which encode components of the mismatch enzyme repair system may cause HNPCC. To determine the extent and nature of locus heterogeneity in HNPCC, we performed genetic linkage studies in 14 HNPCC families from eastern and north-western England. Linkage to hMLH1 was excluded in six families, each of which were likely to be linked to hMSH2 (lod score > 1.0 in each family and total lod score for all six families = 7.64). Linkage to hMSH2 was excluded in three families, each of which were likely to be linked to hMLH1 (lod score > 1.0 in each family and total lod score at hMLH1 for all three families = 3.93). In the remaining five families linkage to hMSH2 or hMLH1 could not be excluded. These results confirm locus heterogeneity in HNPCC and suggest that, in the population studied, most large families with HNPCC will have mutations in hMSH2 or hMLH1. We did not detect any correlation between clinical phenotype and the genetic linkage results, but a Muir-Torre syndrome family excluded from linkage to hMLH1 was likely to be linked to hMSH2 and showed microsatellite instability in a tumour from an affected relative.
 ...
PMID:Genetic linkage analysis in hereditary non-polyposis colon cancer syndrome. 761 41

Hereditary non-polyposis colon cancer (HNPCC) comprises 2-6% of the total colorectal cancer burden. Two families are described that show linkage between the HNPCC susceptibility gene and the markers D2S123 and D2S119 on chromosome 2p, producing multipoint lod scores of 3.62 and 3.83, respectively, in the largest pedigree. In our third family the multipoint lod scores for D2S123 and D2S119, -2.97 and -3.12, excluded localization of a susceptibility gene in this region indicating that there is at least one more gene that causes predisposition to HNPCC. The exclusion was based on at least one genotype for an individual who had multiple primary colon and extracolonic tumours and could not be considered to have had common forms of cancer. Our results therefore encourage further gene mapping to pursue the localization of additional HNPCC genes. These findings confirm the presence of the susceptibility gene for HNPCC, COCA1, on chromosome 2p. They allow the immediate identification of a subset of HNPCC families, and provide the means for presymptomatic testing of family members if sufficient number of members are available for study.
 ...
PMID:Chromosome 2p linkage analysis in hereditary non-polyposis colon cancer. 762 99

Genetic predispositions to colorectal cancer can schematically be divided in two categories depending on the presence or absence of a diffuse polyposis i.e.: a large number of adenomatous polyps in the colon and rectum of affected patients. These syndromes are referred as familial adenomatous polyposis coli and hereditary non polyposis colon cancer (HNPCC) respectively. The gene which when altered causes familial adenomatous polyposis coli is called APC and has been identified in 1991 but the function of its product remained elusive. Recent experimental data indicate that the APC protein can interact with catenins and tubulins, two groups of proteins known to be components of adherens junctions and cytoskeleton. Thus the APC protein may play a role in cell adhesion and in transduction of signal regulating the cell cycle. Of more immediate clinical interest is the observation that specific APC mutations appear to participate in the severity of the disease and determine the development of hypertrophy of the retinal pigment epithelium, a diagnostically important manifestation of the APC disease found in 70% of the patients. HNPCC syndromes have been recognized as being frequently associated with a defect in the DNA mismatch repair pathway. Furthermore, human genes, demonstrating homology with the bacterial DNA repair genes MutS and MutL, have been identified and shown to be altered in several HNPCC families. There are now indications that genotyping of tumor DNA at particular loci, termed microsatellite, may contribute in the identification of patients genetically predisposed to tumor development.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Genetic predispositions to colorectal cancer. 767 42

Escherichia coli methyl-directed mismatch repair eliminates premutagenic lesions that arise via DNA biosynthetic errors; components of the repair system also block ectopic recombination between diverged DNA sequences. A mismatch-dependent, methyl-directed excision reaction that accounts for function of the system in replication fidelity has been reconstituted in a purified system dependent on ten activities. The reaction displays a broad specificity for mismatched base pairs and is characterized by an unusual bidirectional excision capability. Human cell nuclear extracts support strand-specific mismatch correction in a reaction that is similar to bacterial repair, with respect to both mismatch specificity and unusual features of mechanism. Like the bacterial system, the human pathway also functions in mutation avoidance because several classes of mutator human cells are deficient in the reaction. These include an alkylation-tolerance cell line that is resistant to the cytotoxic action of N-methyl-N'-nitro-nitrosoguanidine, as well as hypermutable RER+ tumour cells such as those associated with hereditary non-polyposis colon cancer. In vitro experiments indicate that the human repair reaction is dependent on at least six activities, excluding DNA ligase, and that distinct defects in the system can lead to the RER+ phenotype.
 ...
PMID:Mismatch repair, genetic stability and tumour avoidance. 774 60

A hereditary form of colon cancer, hereditary non-polyposis colon cancer (HNPCC), is characterized by high instability of short repeated sequences known as microsatellites. Because the genes controlling microsatellite stability were known in bacteria and yeast, as was their evolutionary conservation, the search for human genes responsible for HNPCC became a 'targeted' search for known sequences. Mismatch-repair deficiency in bacteria and yeast produces multiple phenotypes as a result of its dual involvement in the editing of both replication errors and recombination intermediates. In addition, mismatch-repair functions are specialized in eukaryotes, characterized by specific mitotic (versus meiotic) functions, and nuclear (versus mitochondrial) localization. Given the number of phenotypes observed so far, we predict other links between mismatch-repair deficiency and human genetic disorders. For example, a similar type of sequence instability has been found in HNPCC tumours and in a number of neuro-muscular genetic disorders. Several human mitochondrial disorders display genomic instabilities reminiscent of yeast mitochondrial mismatch-repair mutants. In general, the process of mismatch repair is responsible for the constant maintenance of genome stability and its faithful transmission from one generation to the next. However, without genetic alteration, species would not be able to adapt to changing environments. It appears that nature has developed both negative and positive controls for genetic diversity. In bacteria, for example, an inducible system (sos) exists which generates genetic alterations in response to environmental stress (e.g. radiation, chemicals, starvation). Hence, the cost of generating diversity to adapt to changing conditions might be paid as sporadic gene alterations associated with disease.
 ...
PMID:Editing DNA replication and recombination by mismatch repair: from bacterial genetics to mechanisms of predisposition to cancer in humans. 774 61

Very recently a new molecular mechanism in the tumorigenesis of colorectal carcinoma has been described which is closely linked to hereditary non-polyposis colonic cancer (HNPCC). Ubiquitous changes in the length of simple repetitive DNA sequences between constitutional and tumour DNA occur in about 90% of cases of HNPCC and in about 15% of cases of non-familial, sporadic colorectal carcinoma. Such microsatellite instabilities have been shown to be the phenotypical marker of mutations in the human homologues of prokaryotic mismatch repair genes (MutS, MutL, MutH). These data provide crucial new tools in the detection of patients at high risk of developing colon cancer and other HNPCC-related carcinomas. In addition, these developments provide new insights into a new, presumably primary event in oncogenesis, i.e. the occurrence of mutations in genomic stability genes leading to an increased cellular mutation rate ("mutator phenotype") and thus to cancer.
 ...
PMID:Microsatellite instability: new aspects in the carcinogenesis of colorectal carcinoma. 777 99

Familial adenomatous polyposis (FAP) is characterized by the presence of premalignant adenomas of the large and small bowel. Prophylactic colectomy deals with the risk for colon cancer, leaving duodenal cancer as the leading cause of death. Although most FAP patients have duodenal adenomas, only approximately 5% develop duodenal cancer. This study looks at progression of duodenal polyps with time. The outcome of endoscopic surveillance in the duodenum of 70 patients with familial adenomatous polyposis was determined. A mean of 40 months elapsed between endoscopies. Outcome was measured using video comparison and a staging system that includes histological assessment. Duodenal cancer developed in one patient, and was suspected in two others. The stage of duodenal polyposis worsened in another seven patients. When histology was ignored, comparison of video recordings in 52 patients showed a worsening in 21 (40%). In conclusion, further surveillance appears warranted so that patients at high risk for duodenal cancer might receive early treatment. Should slow progression of duodenal polyposis be shown to be associated with low risk, then most patients can be safely offered less frequent endoscopies than hitherto.
 ...
PMID:Surveillance of duodenal polyps in familial adenomatous polyposis: progress report. 783 98

Hereditary colon cancer is caused by mutations in several different loci. The APC gene on chromosome 5 causing adenomatous polyposis coli represents a minority of the inherited colon cancer cases, while hereditary-non polyposis colon cancer (HNPCC) may cause five percent of all human colon cancer. One gene causing HNPCC was recently mapped to chromosome 2 but the same study also showed that at least one additional locus may cause HNPCC. We now present tight linkage between a polymorphic marker on the short arm of chromosome 3 and the disease locus, and find that these families also manifest signs of a general DNA replication disorder.
 ...
PMID:Genetic mapping of a second locus predisposing to hereditary non-polyposis colon cancer. 790 89


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