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)

The gene for familial adenomatous polyposis coli (APC or FAP), which has previously been linked to chromosome 5q21 has been identified. The APC gene has been found to be altered by point mutations in the germ line of both adenomatous polyposis coli and Gardner's syndrome patients and somatically in tumors from sporadic colorectal cancer patients. During the hunt for the APC gene, the closely linked MCC (mutated in colorectal cancer) gene was identified and found to be altered somatically in tumors from sporadic cancer patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal carcinogenesis and that mutations at the APC gene can cause both adenomatous polyposis coli and Gardner's syndrome. The identification of these genes should aid in the counseling of patients with genetic predispositions to colorectal cancer. Progress has also been made in identifying specific genetic changes that occur in other gastrointestinal cancers. A mutational "hotspot" in the p53 gene in human hepatocellular carcinomas has been identified that could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1.
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PMID:Cell and molecular biology of gastrointestinal tract cancer. 132 39

The Singapore Polyposis Registry was established in 1989 in Singapore General Hospital. The aim is to provide a central registry service to all doctors in Singapore to facilitate in identification, surveillance and management of families and individuals at high risk of getting colorectal cancer from FAP (Familial Adenomatous Polyposis) and HNPCC (Hereditary Non-polyposis Colorectal Cancer). Both have an autosomal dominant inheritance that gives rise to colorectal cancer at any early age if untreated. They account for 5-6% of all colorectal cancers. Sixteen FAP families with 139 members have been evaluated. Fifty-eight members are affected and 81 are at risk or unaffected. Those who have been screened positive have a much lower risk of cancer (13%) compared with those who presented with the disease (89%) and death from colorectal cancer in the corresponding groups were nil and 58%. Eight HNPCC families with 36 affected and 170 at-risk members have been registered. Colonoscopic surveillance have just started: one case of Dukes' A cancer in a 26 year-old patient, and two cases with polyps have been diagnosed. Advances in molecular genetics and the identification of APC (Adenomatous Polyposis Coli) gene in the FAP locus of Chromosome 5 have made it possible to diagnose FAP genetically. This has important impact on management in terms of prenatal diagnosis and dietary and chemoprevention programmes in addition to surgical intervention.
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PMID:The Singapore Polyposis Registry. 132 51

The aim of this study was to develop a method for quantitation of APC mRNA and to measure APC mRNA levels in human tissues. This was done using a competitive reverse transcription PCR with a synthetic RNA control. APC mRNA (pg/microgram total RNA) was quantitated in the following tissues: normal colon 133.6 +/- 69.0; normal duodenum 16.6 +/- 15.7; normal thyroid 30.4 +/- 20.3; normal esophagus 65.2 +/- 58.8; colonic carcinoma 66.5 +/- 30.3; esophageal carcinoma 54.7 +/- 26.5; papillary thyroid carcinoma 55.8 +/- 32.9 and colonic adenomas from patients with familial adenomatous polyposis 46 +/- 15. APC mRNA levels were significantly lower in the duodenum and thyroid than in the colon and esophagus. The quantity of APC mRNA was lower in colonic adenomas from FAP patients than in normal colonic mucosa (p < 0.05).
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PMID:Quantitation of APC mRNA in human tissues. 750 12

An earlier study has shown that FAP patients with mutations in codons 136-302 of the APC gene do not develop congenital hypertrophy of the retinal pigment epithelium (CHRPE), whereas those with mutations in codons 463-1387 regularly do. Here we present data on 36 patients from 20 families with mutations in codons 1445-1578. These patients lack CHRPE. Furthermore, with the exception of three prepubertal children all patients with mutations in codons 1445-1578 developed desmoid tumours. This relationship between certain extracolonic manifestations and site of the APC mutation points to a specific role of the APC protein in different tissues.
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PMID:Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. 779 85

In Japan 1052 FAP patients in 688 family trees have been registered at the National Polyposis Center. In Hamamatsu University School of Medicine, we have been treating 50 patients in 28 family trees. Among these families, we analysed the site of mutations of the APC gene, which so far has been clarified in 21 family trees. Presymptomatic diagnosis was possible in 12 individuals among the carriers in 6 FAP families. Most of the mutations were clustered within the 5'half of exon 15. There was no correlation between extra colonic phenotypic expression and site of mutation, however, the desmoid should be studied further, as the number of cases was limited.
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PMID:Identification of germ line mutation of APC gene in possible carriers of familial adenomatous polyposis (FAP). 784 May 21

Heterogeneity among and within FAP pedigrees for the age of symptom onset and the age at death from colorectal cancer was studied in a sample of 583 patients of the Italian Polyposis Registry. The among pedigree variation was largely explained by clustering of families in two groups, 'early FAP' (most colorectal cancer deaths below 45 years of age) and 'late FAP' families (most deaths above age 45). The within-family variation was explained by a marked phenomenon of anticipation (15 years per generation, on the average), possibly not due to ascertainment bias. We then considered the pedigrees with identified mutation in the APC gene. Six families shared a common deletion at codon 1309 and showed the early FAP phenotype. Two families shared a mutation at codon 1061 and revealed the late FAP phenotype. Another two families (codons 453 and 302) clustered with the late FAP group, whereas a family with mutation at codon 835 clustered with the early FAP group. We suggest that there are at least two classes of mutations in the APC gene with different consequences at the phenotypic level. It seems that there are several critical points within the APC protein sequence at which truncation causes a more aggressive disease than truncation at other points.
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PMID:Age of onset in familial adenomatous polyposis: heterogeneity within families and among APC mutations. 786 89

Owing to the large size of the APC gene, responsible for familial adenomatous polyposis, direct screening for individual mutations is not a practical approach. In the present study we establish the methodology of fluorescence based semi-automated DNA analysis to perform presymptomatic diagnosis of members at risk from 11 Portuguese FAP families with three (CA)n markers flanking the APC gene, MBC, CB26, and YN5.64, and four intragenic RFLPs. Haplotypes were constructed on the basis of individual genotypes and their segregation through generations were followed. The study was informative for 12% of subjects using only intragenic RFLPs and increased to 90% when we used the three (CA)n flanking markers. We report two of the 11 families under study in our laboratory and show recombinant events leading to a precise localisation of the CB26 marker between D5S82 and the APC gene. In one family there was a loss of (CA) units of one allele of the CB26 marker from an unaffected mother to her son.
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PMID:Presymptomatic diagnosis in Portuguese FAP families using intragenic RFLPs and (CA)n flanking markers by fluorescence based semiautomated DNA analysis. 872 2

Germline mutations of the adenomatous polyposis coli gene are associated with the dominantly inherited syndrome of familial adenomatous polyposis. Somatic mutations in this gene are an early event in sporadic colorectal tumorigenesis. Here we report a family with genetic characteristics that do not conform exactly to either of these situations. The index case and three siblings presented with colorectal cancer, and another sibling had lung cancer. There was no evidence of colorectal cancer susceptibility in previous generations, although one case of gastric cancer was observed. Using restriction fragment length polymorphism, single-strand conformational polymorphism, and sequencing analysis, we screened each living family member for alterations in the mutation cluster region of exon 15 of the APC gene. A constitutional single base pair substitution at codon 1317 was observed in two of the siblings with colorectal cancer, but neither exhibited any colonic features typical of FAP nor an early onset of cancer. This constitutional change is a missense mutation and therefore does not result in the truncation of the APC protein, the most commonly observed result of mutation in this gene. We present evidence that this change is not a polymorphism and may be capable of conferring a growth advantage. This particular germline APC mutation does not completely cosegregate with cancer in this family; therefore, we conclude that another gene locus may be responsible for the increased cancer risk observed.
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PMID:Germline APC mutation (Gln1317) in a cancer-prone family that does not result in familial adenomatous polyposis. 883 76

Desmoid tumors are slowly growing fibrous tumors highly resistant to therapy and often fatal. Here, we report hereditary desmoid disease (HDD), a novel autosomal dominant trait with 100% penetrance affecting a three-generation kindred. Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early development of premalignant adenomatous polyps in the colorectum due to chain-terminating mutations of the APC gene. In general, one or more members in approximately 10% of the FAP families manifest desmoid tumors. Affected individuals from the HDD kindred are characterized by multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Osteomas, epidermal cysts, and other congenital features were also observed. We show that HDD segregates with an unusual germ-line chain-terminating mutation at the 3' end of the APC gene (codon 1924) with somatic loss of the wild-type allele leading to tumor development.
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PMID:Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene. 894 Feb 62

Recent knowledge about biological role of tumor suppressor genes and their products: RB1, p53, WT1, DCC, APC/FAP, NF1, NF2, VHL, MCC and MTS1 is presented. The main approaches of these agents as physiological regulators of cell growth and proliferation are discussed. Views on the tumor suppressor genes involvement in the development of inherited and sporadic forms of cancer have been reviewed.
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PMID:[Antioncogenes--tumor suppression genes]. 933 80


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