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)

Familial adenomatous polyposis (FAP), which includes familial polyposis coli (FPC) and the Gardner syndrome (GS), is a genetically determined premalignant disease of the colon inherited by a locus (APC) mapping within 5q15-q22. To elucidate the role of 5q loss in FAP tumorigenesis, we analysed 51 colorectal tumors and seven desmoids from 19 cases of FPC and five GS patients, as well as 15 sporadic colon cancers. RFLP analysis revealed a high incidence of allelic deletion in hereditary colon cancers as well as in sporadic colon cancers with a peak at the APC locus. APC loss resulted primarily from interstitial deletion or mitotic recombination. Combined tumor and pedigree analysis in a GS family revealed loss of normal 5q alleles in three tumors, including a desmoid tumor, which suggests the involvement of hemizygosity or homozygosity of the defective APC gene in colon carcinogenesis and, possibly, in extracolonic neoplasms associated with FAP.
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PMID:Molecular nature of chromosome 5q loss in colorectal tumors and desmoids from patients with familial adenomatous polyposis. 217 53

Familial adenomatous polyposis (FAP) is associated with a number of extraintestinal manifestations, which include osteomas, epidermoid cysts, and desmoid tumors, often referred to as "Gardner syndrome." Recent studies have suggested that some of the phenotypic features of FAP are dependent on the position of the mutation within the APC gene. In particular, the correlation between congenital hypertrophy of the retinal pigment epithelium (CHRPE) and APC genotype indicates that affected families may be divided into distinct groups. We have investigated the association between the dentoosseous features of GS on dental panoramic radiographs (DPRs) and APC genotype in a regional cohort of FAP families. DPRs were performed on 84 affected individuals from 36 families, and the dento-osseous features of FAP were quantified by a weighted scoring system. Significant DPR abnormalities were present in 69% of affected individuals. The APC gene mutation was identified in 27 of these families, and for statistical analysis these were subdivided into three groups. Group 1 comprised 18 affected individuals from seven families with mutations 5' of exon 9; these families (except one) did not express CHRPE. Groups 2 comprised 38 individuals from 16 families with mutations between exon 9 and codon 1444, all of whom expressed CHRPE. Group 3 comprised 11 individuals from four families with mutations 3' of codon 1444, none of whom expressed CHRPE. Families with mutations 3' of codon 1444 had significantly more lesions on DPRs (P < .001) and appeared to have a higher incidence of desmoid tumors. These results suggest that the severity of some of the features of Gardner syndrome may correlate with genotype in FAP.
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PMID:Severe Gardner syndrome in families with mutations restricted to a specific region of the APC gene. 748 67

Familial adenomatous polyposis (FAP) is a dominantly inherited genetic disorder predisposing to colon cancer through the early development of multiple adenomatous polyps in the large bowel. FAP is not restricted to the colon and rectum, but is a more complex disease which can potentially affect almost any organ not only with benign tumours but also with life threatening carcinomas. Desmoid tumours and gastroduodenal polyps and cancer are the two more worrying extracolonic manifestations of FAP. Recent advances in FAP knowledge, such as the report of congenital hypertrophy of the retinal pigment epithelium (CHRPE) or the APC gene identification, are very useful for screening and long-term follow-up of the patients through regional or national registries. Nutritional and pharmacological intervention trials are under way to assess potential new medical treatments of FAP. Surgery is still the only effective treatment for colorectal cancer prevention in FAP. The choice of a surgical procedure is controversial, but the introduction of total proctocolectomy with ileal pouch-anal anastomosis can be considered as a major advance in surgical treatment of FAP during the last decade.
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PMID:The clinical [corrected] background of familial adenomatous polyposis. History, epidemiology, diagnosis and treatment. 757 88

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

Familial adenomatous polyposis coli is caused by constitutional mutations in the APC gene. The hallmark of familial adenomatous polyposis coli is the presence of numerous (> 100) colorectal polyps, but mutations in the 5' end of the APC gene have been associated with familial colorectal cancer without florid polyposis. Although familial adenomatous polyposis coli accounts for only a minority of familial colorectal cancer cases, we hypothesised that APC mutations which were not associated with florid polyposis might make a significant contribution to nonpolyposis familial colorectal cancer. To investigate this possibility, we analysed 40 unrelated patients with familial colorectal cancer without classical familial adenomatous polyposis coli for mutations in exons 1 to 6 (codons 1 to 243) of the APC gene. No mutations were detected, but a C-->T polymorphism at nucleotide 333 (Arg-->Trp at codon 99) was identified. No 5' APC mutations were detected in two patients with desmoid tumours and a family history of colorectal cancer and polyps. We conclude that mutations in exons 1 to 6 of the APC gene are infrequent in patients with familial colorectal cancer who do not have many colorectal polyps.
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PMID:Molecular genetic analysis of exons 1 to 6 of the APC gene in non-polyposis familial colorectal cancer. 883 24

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

Desmoid tumours are generally very rare but occur about 100 times more frequently in the colorectal cancer predisposition syndrome familial adenomatous polyposis (MIM 175100), being represented in about 10% of patients. In addition to desmoid disease occurring in familial adenomatous polyposis (FAP) there exist familial infiltrative fibromatosis (MIM 135290) kindreds where there is no evidence of FAP. Previously we have described a kindred with familial infiltrative fibromatosis (FIF) in which desmoid tumours were associated with nonpolyposis colorectal cancer. FAP is caused by mutations in the APC gene and various genotype-phenotype relationships have been defined including reports that colorectal polyposis is less severe with mutations 5' to codon 157 and that the risk of desmoid tumours is high in FAP patients with APC gene mutations between codons 1444 and 1598. There is relatively little information on the phenotype of APC gene mutations 3' to codon 1598; however, one large family has been reported with a mutation at codon 1987 which presents with a highly variable phenotype which includes desmoid disease. We screened our original FIF kindred and three further families with a similar phenotype for mutations in the APC gene. A 4 bp frameshift deletion in codon 1962 was identified in the original FIF kindred and two further apparently unrelated families. Haplotype analysis suggests a common origin for the APC mutation in all three families. Affected individuals had no evidence of congenital hypertrophy of the retinal pigment epithelium. Colorectal polyposis was variable, and most affected patients had either none or a few late onset polyps. These findings demonstrate (i) that FAP and FIF are allelic, and (ii) that APC gene mutations which truncate the APC protein distal to the beta-catenin binding domain are associated with desmoid tumours, absent CHRPE and variable but attenuated polyposis expression.
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PMID:Familial infiltrative fibromatosis (desmoid tumours) (MIM135290) caused by a recurrent 3' APC gene mutation. 896 44

Clinical desmoid disease affect approximately 10 per cent of patients with familial adenomatous polyposis (FAP); the subclinical rate is unknown. Desmoids are probably neoplastic rather than regenerative in origin and may arise in association with germline or somatic mutations at or beyond codon 1444 of the APC gene. Intra-abdominal desmoids behave unpredictably but are an important cause of death in those with FAP. Signal intensity on magnetic resonance imaging reflects tumour cellularity, which in part determines progression, and this may help management. Surgical treatment of advanced desmoids is hazardous, but medical treatments have limited success. Chemotherapy with doxorubicin and dacarbazine is currently under evaluation.
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PMID:Desmoids in familial adenomatous polyposis. 917 77

Familial adenomatous polyposis coli (FAP) has been shown to be associated with germline mutations of the adenomatous polyposis gene (APC) on chromosome 5. Extra-colonic manifestations also occur in FAP and include desmoid tumors, epidermoid cysts and osteomas. The combination of FAP with extracolonic symptoms is commonly referred to as Gardner's syndrome. It remains difficult, however, to predict which patients may have a propensity to develop extracolonic manifestations. The rapid acetylation phenotype is believed to be associated with an increased likelihood of sporadic colorectal cancer, whereas the slow acetylation phenotype is recognized as a predisposing factor for bladder cancer. The slow acetylation phenotype is caused by mutant alleles of the cytosolic enzyme N-acetyltransferase (NAT2). In this study, we determined the NAT2 genotype in members of one large FAP family and three smaller ones all of which had been shown to harbor the same germline APC gene mutation. We observed a significant correlation between slow acetylation genotypes and extracolonic manifestations of the disease. Rapid acetylation genotypes were not overrepresented in colorectal cancer cases in this family as compared to the frequency of this genotype in the normal Caucasian population.
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PMID:Association of extracolonic manifestations of familial adenomatous polyposis with acetylation phenotype in a large FAP kindred. 915 20


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