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)

Several rodent studies based on molecular biology have suggested that accumulation of genetic alterations in cancer-associated genes is required to convert a normal cell into a malignant cell. Activation of oncogenes and inactivation of tumor suppressor genes appear to be involved in carcinogenesis. In renal cell carcinomas, we have recently implied that the presence of tumor suppressor genes at chromosome 3p13-14.3 and 21.3, the regions where are also commonly deleted in adenocarcinoma of the lung; at chromosome 5q21, the region where the MCC (mutated in colorectal cancer) gene and APC (adenomatous polyposis coli) gene are located; at chromosome 6q27; and at 10q 21-23. We have also indicated that genes on 3p is probably important for development of RCCs and genes on 5q, 6q, and 10q may be associated with progression of RCCs.
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PMID:[Tumor suppressor genes associated with development of human renal cell carcinoma]. 149 60

The tumor suppressor gene APC was recently identified, and the cDNA was cloned from chromosome 5q21. Point mutations affecting APC are seen in the hereditary syndrome familial adenomatous polyposis, and point mutations in APC and a closely linked gene, MCC, as well as loss of heterozygosity involving chromosome 5q have been reported in sporadic colon cancer. To our knowledge, loss of heterozygosity involving APC or MCC or both has not yet been described in any other human cancer besides lung cancer. We used the polymerase chain reaction and DNA content flow cytometric nuclear sorting to examine 30 primary human esophageal cancers for loss of heterozygosity of APC or MCC or both. Loss of one allele was detected in 77% of 26 informative cases. These data suggest that loss of heterozygosity of regions on 5q including the APC and MCC genetic loci is involved in the development and/or progression of most human esophageal cancers. They imply that inactivation of APC, MCC, and/or a linked gene on chromosome 5q plays a role in the pathogenesis of some cancers of the upper gastrointestinal tract, as well as in colon cancer and familial adenomatous polyposis.
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PMID:Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers. 156 31

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common form of hereditary colon cancer. Autosomal dominant inheritance is evident from pedigrees but the genetic basis of the disorder is otherwise unknown. Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and APC was shown to be the gene predisposing to familial adenomatous polyposis. To determine if these genes also confer susceptibility to HNPCC we performed linkage analyses in nine affected families. The MCC-APC region could be formally excluded as the locus for HNPCC in seven families. In one family the results were suggestive of exclusion, although they were not conclusive. The remaining family was uninformative. We used two alternative definitions of affected status. Based on haplotypes for MCC and APC the added pairwise logarithm-of-odds score for all nine families was -22.57 at the recombination fraction of 0.00 using more stringent criteria for the HNPCC phenotype and -22.67 for less stringent criteria. In addition to blood DNA samples from living family members, DNA from formaldehyde-fixed archival pathology specimens from decreased individuals contributed to these linkage results.
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PMID:Evidence that the MCC-APC gene region in 5q21 is not the site for susceptibility to hereditary nonpolyposis colorectal carcinoma. 164 45

Recent studies suggest that one or more genes on chromosome 5q21 are important for the development of colorectal cancers, particularly those associated with familial adenomatous polyposis (FAP). To facilitate the identification of genes from this locus, a portion of the region that is tightly linked to FAP was cloned. Six contiguous stretches of sequence (contigs) containing approximately 5.5 Mb of DNA were isolated. Subclones from these contigs were used to identify and position six genes, all of which were expressed in normal colonic mucosa. Two of these genes (APC and MCC) are likely to contribute to colorectal tumorigenesis. The MCC gene had previously been identified by virtue of its mutation in human colorectal tumors. The APC gene was identified in a contig initiated from the MCC gene and was found to encode an unusually large protein. These two closely spaced genes encode proteins predicted to contain coiled-coil regions. Both genes were also expressed in a wide variety of tissues. Further studies of MCC and APC and their potential interaction should prove useful for understanding colorectal neoplasia.
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PMID:Identification of FAP locus genes from chromosome 5q21. 165 62

Previous studies suggested that one or more genes on chromosome 5q21 are responsible for the inheritance of familial adenomatous polyposis (FAP) and Gardner's syndrome (GS), and contribute to tumor development in patients with noninherited forms of colorectal cancer. Two genes on 5q21 that are tightly linked to FAP (MCC and APC) were found to be somatically altered in tumors from sporadic colorectal cancer patients. One of the genes (APC) was also found to be altered by point mutation in the germ line of FAP and GS patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS. The identification of these genes should aid in understanding the pathogenesis of colorectal neoplasia and in the diagnosis and counseling of patients with inherited predispositions to colorectal cancer.
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PMID:Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. 165 63

We have isolated several genes in the chromosome 5q21 region tightly linked to hereditary familial polyposis coli (FAP) and Gardner's syndrome (GS). Two of these genes (MCC and APC) were found to be somatically altered by point mutation, deletion or insertion in tumors of sporadic colorectal cancer patients. One of them (adenomatous polyposis coli; APC) was also found to mutate in the germ-line of both APC and GS patients. The identification of these genes has significant implications for understanding the pathogenesis of colorectal neoplasia and for the diagnosis and counseling of individuals with inherited predispositions to colorectal cancer. Furthermore, in one colon carcinoma, we identified an interesting mechanism causing dysfunction of the APC gene. This gene was disrupted by a somatic insertion of a long interspersed repetitive element (LINE-1 sequence: L1) into the last exon. As an insertional sequence contains a 3' portion of the L1 consensus sequence including the poly(A) tract and an 8 bp target-site duplication was observed, this insertion is suspected to be caused by a retrotranscriptional insertion of one of the L1 sequences. This is the first case of the disruption of a tumor suppressor gene by the insertion of a movable genetic element.
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PMID:Mutations of the adenomatous polyposis coli gene in familial polyposis coli patients and sporadic colorectal tumors. 166 88

Colorectal cancer affect the 15% of general population in developed countries. Cancer is a multistep process in which multiple genetic alterations must usually occur in several years. The premalignant step consists of one or multiple aberrant crypts due to hyperproliferation of cells and its shift from the deep third of the crypt to its surface. It has been suggested that abnormality in the APC gene is responsible for this. Furthermore, there exists DNA hypometilation, activation of the gene K-ras and ornithine decarboxylase activity. There is also a loss of MCC gene, that seems to interact with the APC gene. Entire alterations described make possible the Class I adenoma formation. This adenoma, needs the loss of the DCC gene (late stage in the carcinogenesis process), to become a Class II adenoma. The following alteration is deleted and mutation of the p53 gene. There is also an activation of the c-myc oncogene. These two genes are important mechanisms for the conversion of a benign adenoma to a malignant one, adenoma with in situ carcinoma or Class III adenoma. This type of adenoma becomes carcinoma and metastatic stage, throughout inactivation of several tumor suppressor genes. Besides the hereditary APC alteration and other acquired genetic changes as described above there are other associated genetics, antigenics, and enzymes that have an important role in the adenoma-carcinoma sequence. Several carcinogenic factors have been described which also contribute in the adenoma and carcinoma formation: ulcerative colitis, acromegaly, familial history of colonic neoplasia, certain professions, smoking and drinking, consumption of red or processed meat, etc.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Etiology of colorectal cancer]. 755 83

Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and also shown to be associated with the development of esophageal and lung cancers. To determine if these genes are also involved in the development of gastric cancer, 79 primary human gastric cancers were examined for loss of heterozygosity of APC or MCC or both. Loss of APC was detected in 20% of 15 informative differentiated cases, but not in 20 informative undifferentiated cases, while loss of MCC occurred in 23.5% of 17 informative undifferentiated cases, but not in 19 informative differentiated cases. These data suggest that loss of heterozygosity of APC/MCC gene is involved in the development of gastric carcinomas, and that distinctly different molecular mechanism(s) may be responsible for the development of differentiated and undifferentiated gastric carcinomas.
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PMID:Loss of heterozygosity of APC/MCC gene in differentiated and undifferentiated gastric carcinomas in Taiwan. 758 53

The correlation between the mutation spectra of tumor suppressor genes Rb, p53, APC and MCC in human esophageal cancer (EC) and in human and monkey esophageal epithelium treated with N-Methyl-N-Benzyl nitrosamine (NMBzA) was studied using PCR amplification and direct sequencing methods. The results showed that in 40.9% (9/22) of the specimen examined, the mutation spectrum of p53 in primary EC was similar to that in the esophageal epithelium of human fetus (in vitro) and monkey (in vivo) treated with NMBzA. The same mutational spectra of tumor suppressor genes Rb, APC, MCC in esophageal epithelium cells of human and monkey treated with NMBzA were also found in some human primary EC. The correlation observed in the mutation spectra of multiple tumor suppressor genes between human primary EC and the esophageal epithelia of human and monkey origin treated with NMBzA wouldsuggest that NMBzA may be the esophageal etiological agent for human esophageal cancer in China.
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PMID:[Correlation studies on the alterations of multiple tumor suppressor genes in human esophageal cancer and in human and monkey esophageal epithelial cells treated with N-methyl-N-benzyl nitrosamine]. 758 88

The mutation and deletion of APC, MCC genes in human esophageal cancer were analyzed by PCR amplification and direct sequencing assay. In PCR amplification analysis, one of 10 cases of esophageal cancer was found to have APC gene deletion in exon 11; one of 10 cases of EC was found to have MCC gene deletion in exon 12; one case of EC was found to have MCC gene deletion in exon 12. One of adjacent non-tumor tissue was also found to have deletion at exon 12 of MCC. In PCR direct sequencing analysis, two of 10 cases of EC were found to contain APC gene mutation in exon 11, two of 7 cases of EC were found to contain MCC genes mutation in exon 12. The results confirmed that mutation of APC and MCC genes exists in human esophageal cancer. It gives new clues to the understanding of carcinogenesis of human esophageal cancer. The mechanism of mutation or deletion of APC and MCC genes in EC needs further study.
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PMID:[Mutation of tumor suppressor genes APC and MCC in human esophageal cancer]. 765 96


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