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 APC gene is responsible for familial adenomatous polyposis and is considered to be a tumor suppressor gene associated with development of sporadic colorectal tumors. Here we report the disruption of the APC gene caused by somatic insertion of a long interspersed repetitive element (LINE-1 sequence) into the last exon of the APC gene in a colon cancer. The inserted sequence was composed of a 3' portion of the LINE-1 consensus sequence and nearly 180 base pairs of polyadenylate tract. Furthermore, since an 8-base pair target site duplication was observed, retrotranscriptional insertion of an active LINE-1 sequence is suspected as the cause of this insertion event. This is the first report of the disruption of a tumor suppressor gene caused by somatic insertion of a mobile genetic element.
Cancer Res 1992 Feb 01
PMID:Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. 131 68

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

Most adenocarcinomas of the colorectum arise in a visible benign precursor lesion, the adenoma, which is a monoclonal proliferation of dysplastic nonmalignant epithelial cells. The resultant adenoma-adenocarcinoma sequence represents the predominant pathogenetic pathway, in contrast to de novo carcinoma. Therefore, the adenoma is a tempting endpoint for chemoprevention trials. The adenoma-adenocarcinoma sequence occurs in diverse clinical settings. In familial adenomatous polyposis (FAP) syndrome, autosomal dominant inheritance of the mutated APC (adenomatous polyposis coli) gene on chromosome 5q21 typically results in thousands of adenomas in the colorectum and in lesser numbers in the proximal small bowel. Adenocarcinoma usually develops in only a few of these adenomas, typically in the left colon and duodenum. In hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, autosomal dominant inheritance of an unidentified gene appears to result in small numbers of adenomas which progress frequently to adenocarcinoma, predominantly in the right or transverse colon. In familial aggregation of colorectal cancer without a recognizable syndrome, cancer and/or adenomas occur in pedigree members. In "sporadic" cancers and adenomas, family history is absent and the tumors are mainly in the left colon. Colorectal adenomas have variable characteristics including size, shape (polypoid vs. flat), villous architecture, and dysplasia. A variety of oncogenes and tumor suppressor genes are altered during progression. Epigenetic factors are important as evidenced by the disappearance of adenomas in FAP patients after ileorectal anastomosis or treatment with the nonsteroidal antiinflammatory drug sulindac. Several variations on the theme of the adenoma-carcinoma sequence are evident. Identification of the inherited and acquired genetic alterations as well as the interacting environmental factors will provide a rational basis for chemoprevention.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The adenoma-adenocarcinoma sequence in the large bowel: variations on a theme. 133 99

The MCC gene is a candidate as a tumor suppressor gene for colorectal neoplasms. Further, MCC is tightly linked to the familial adenomatous polyposis (FAP) locus by linkage and physical analysis. Hence, restriction fragment length polymorphisms (RFLPs) of this gene might be very useful for presymptomatic diagnosis of individuals in families segregating mutant alleles of the APC gene. Here we report the identification of five polymorphic systems in MCC gene (both cDNA and genomic), one of which is an insertion/deletion polymorphism that is detectable by a polymerase chain reaction method. These five RFLP systems should be useful for linkage studies in FAP and for examining loss of heterozygosity at this locus in colonic polyps and tumors.
Jpn J Cancer Res 1992 Jan
PMID:Insertion/deletion polymorphism and other restriction fragment length polymorphisms in the MCC gene. 134 24

Carcinogenesis is a multistage process that has been characterized both by the activation of cellular oncogenes and by the loss of function of tumor suppressor genes. Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. Hybrids containing chromosome 18 are morphologically similar to the parental line, whereas those containing chromosome 5 are morphologically distinct from the parental cell line, being small, polygonal, and tightly packed. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Introduction of chromosome 5 had little to no effect on responsiveness, whereas transfer ot chromosome 18 restored responsiveness to some degree. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro.
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PMID:Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer. 134 43

Using single-strand conformation polymorphism we have found two polymorphic sites, AAC to AAT at codon 511 (exon 12) and GCT to GCG at codon 708 (exon 15), in the MCC gene. These sites and an RsaI polymorphic site in APC allowed us to study 23 human small cell lung cancer (SCLC) and 7 non-small cell lung cancer samples for allele loss. Of the 23 SCLC samples, 21 (91%) were informative for one or more of these markers, and we found allele loss in more than 80% (17 of 21). In non-small cell lung cancer samples, 5 of 7 (71%) were informative, and reduction or loss of one allele was found in 2 of 5 (40%). Seven cases were informative for both genes, loss of heterozygosity occurred for both genes in five, one retained heterozygosity for both, and one SCLC had loss of heterozygosity for APC but not for MCC. We conclude that loss of heterozygosity occurs frequently for MCC and APC in lung cancer of all histological types and is very frequent in SCLC. This suggests the presence of tumor suppressor gene(s) in the MCC/APC region of 5q21 involved in human lung cancer.
Cancer Res 1992 Apr 01
PMID:Polymorphic sites within the MCC and APC loci reveal very frequent loss of heterozygosity in human small cell lung cancer. 134 17

Loss of heterozygosity occurring on various chromosomes has been described in the majority of human tumors. The targets of frequent or consistent subchromosomal deletions are believed to be tumor suppressor genes. We examined 72 esophageal tumors (46 squamous cell carcinomas and 26 adenocarcinomas) for loss of heterozygosity at the p53, Rb, APC, MCC, and DCC loci. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing polymerase chain reaction at polymorphic sites within the genes. Loss of heterozygosity occurred in 55% of informative cases at p53, in 48% of informative cases at Rb, in 66% at APC, in 63% at MCC, and in 24% at DCC. Ninety-three % of tumors informative at all loci (fully informative) lost heterozygosity of at least one locus. A high percentage of fully informative tumors (71%) also lost heterozygosity at more than one locus. There were no significant differences among histological types in the prevalence of loss of heterozygosity at any locus. There were correlations of losses involving MCC versus DCC, Rb, and p53. These data suggest that (a) allelic deletions including these tumor suppressor genes are important in the formation and/or progression of most esophageal cancers; (b) allelic deletions involving MCC may not occur independently of deletions involving other tumor suppressor genes; and (c) the accumulation of multiple allelic deletions involving specific tumor suppressor genes may be important in most esophageal tumorigenesis or tumor evolution.
Cancer Res 1992 Dec 01
PMID:Loss of heterozygosity involves multiple tumor suppressor genes in human esophageal cancers. 142 99

The APC (adenomatous polyposis coli) gene is responsible for familial adenomatous polyposis and is also associated with the development of sporadic tumors of the colon and stomach. To investigate whether or not mutations of APC play any role in tumors arising in other organs, we examined somatic mutations of this gene in sporadic (nonfamilial) renal cell carcinomas, hepatocellular carcinomas, and cancers of the lung and pancreas. DNAs isolated from tumors were examined by means of a RNase protection analysis, coupled with the polymerase chain reaction followed by DNA sequencing of the polymerase chain reaction products. By screening a part of the APC coding region, we detected somatic mutations in four of ten pancreatic cancers; each of these mutations would yield a truncated APC product due to a 1- or 5-base pair deletion. These results imply that mutations in APC contribute to carcinogenesis in the pancreas.
Cancer Res 1992 Dec 01
PMID:Frequent somatic mutations of the APC gene in human pancreatic cancer. 142 16

Current recommendations for screening large populations for colorectal neoplasia have been promulgated by a number of researchers and authorities who generally agree that ongoing screening is justifiable in high-risk groups but not yet in average-risk groups. Nonetheless, it is thought to be justifiable to provide screening for average-risk individuals upon request. Choice of tools for screening remains under discussion. Colonoscopy is generally agreed to be justifiable in those patients with the highest risk, ie, members of families with a clear inherited tendency to develop colorectal cancer or those with a personal history of colorectal neoplasia. There is currently no agreement concerning the recommended tools for those with a weaker family history (one or two affected relatives), but regular fecal occult blood testing with occasional limited endoscopic examination of the bowel is usually favored. The new immunochemical-based occult blood tests show great promise for improved sensitivity and specificity. The evidence of the association between Helicobacter pylori gastritis and gastric cancer has been strengthened by three studies that show that patients with gastric cancer are more likely to have had infection in the years (up to 20) prior to diagnosis. The relative risk for cancer when infected with H. pylori is 3.6 to 6, but many H. pylori-positive individuals do not develop gastric cancer and additional factors must be operative. Probably the most exciting development for gastroenterology in 1991 is the identification of the gene on chromosome 5, designated APC, which is responsible for familial adenomatous polyposis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The genetics, epidemiology, and early detection of gastrointestinal cancers. 151 Oct 28


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