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)

Four genetic polymorphisms in the APC and MCC genes at chromosome 5q21 were analysed for loss of heterozygosity (LOH) in 97 primary squamous carcinomas and adenocarcinomas of the lung. LOH was identified in at least two polymorphic loci in 41 percent of informative cases. There was no significant difference in the frequency of LOH between squamous carcinomas and adenocarcinomas. Within the adenocarcinoma group, however, LOH appeared to be more common in tumours having a bronchial origin (5/9; 56 per cent) than in parenchymal adenocarcinoma (6/21; 29 per cent). All 32 tumours showing LOH at one or more polymorphic sites were examined for mutations in the mutation cluster region (MCR) of APC by single-strand conformational polymorphism (SSCP) analysis. Mutations were not detected in any of these cases. We therefore propose that it is likely that a tumour suppressor gene on 5q other than APC is involved in the pathogenesis of lung cancer.
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PMID:Loss of heterozygosity at 5q21 in non-small cell lung cancer: a frequent event but without evidence of apc mutation. 894 12

Previous karyotyping showed an unbalanced translocation between chromosome 3p11.2-p13 and chromosome 5q22 leading to duplication of chromosome 5q22-qter region in nonpapillary renal cell carcinomas. In order to determine the breakpoint at chromosome 5q22 at the molecular level, we have investigated 50 sporadic nonpapillary renal cell carcinomas from consecutive nephrectomies and 24 renal cell carcinomas obtained from two patients with von Hippel-Lindau disease. We used seven DNA markers mapped to and around the APC and MCC genes to detect allelic imbalance. We observed a duplication of chromosome 5q sequences in 11 of 23 informative sporadic tumours and in 18 of 24 hereditary tumours. We determined a breakpoint cluster between the APC and MCC genes at chromosome 5q22. In addition we have found a partial duplication of the smallest overlapping region of about 1.5 Mb sequences including the MCC gene in seven tumours without visible alteration of chromosome 5q in the karyotype. We suggest that this DNA segment harbours a gene or gene cluster, the altered dosage of which is important for the growth of nonpapillary renal cell carcinomas.
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PMID:Duplication of an approximately 1.5 Mb DNA segment at chromosome 5q22 indicates the locus of a new tumour gene in nonpapillary renal cell carcinomas. 907 Jun 58

Multiple gastric cancers, which constitute 4% to 10% of all gastric cancers, occur in older people and are associated with more extensive intestinal metaplasia. With regard to the genesis of multiple gastric cancers, multicentricity (independent origin) rather than multifocality (local or lateral spread of one cancer) has been the favored theory. Conventional morphologic study, however, has not been able to provide convincing evidence in support of multicentricity. The purpose of this study was to verify the multicentric origin of multiple gastric cancers at a genetic level. For this purpose, immunohistochemical and molecular techniques were used to define the mutation pattern of APC, MCC and p53 in multiple lesions of synchronous multiple gastric cancers. The study was based on a total of 30 gastric tumors from 13 patients, including 10 double tumors, 2 triple tumors, and 1 quadruple tumor. Single-strand conformation polymorphism and polymerase chain reaction direct sequencing were carried out for exons 5 to 8 of p53, and loss of heterozygosity was detected on the basis of polymerase chain reaction amplification of polymorphism in exon 10 of MCC and in exon 11 of APC. Twelve of 13 cases showed alteration in one or more genetic markers. Of these, three demonstrated a discordant mutation pattern of p53 in individual lesions, and another two revealed allelic loss of MCC in one lesion and p53 mutation in the other. In six other cases, only one lesion showed alteration of APC, MCC, or p53, and in the remaining case, one lesion carried p53 and MCC mutations and the other carried MCC loss of heterozygosity only. The results of this study showed discordance of the mutation pattern of APC, MCC, and p53 in individual lesions of multiple gastric cancers, providing genetic evidence for a multicentric origin of synchronous multiple gastric carcinomas. Collectively, these findings supported the theory of field cancerization in gastric carcinogenesis.
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PMID:Genetic evidence for the multicentric origin of synchronous multiple gastric carcinoma. 912 Nov 23

The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon cancer carcinogenesis. LOH at this locus has also been described in gastric cancer and preneoplastic lesions. The APC locus has been recently related to a cell surface adhesion molecule and its alteration may favour metastatic dissemination. LOH at 5q21 has been associated with poor prognosis in other tumors such as lung cancer. Thirty-six gastric cancers were evaluated for LOH at 5q21 with 2 polymorphic markers from microdissected paraffin-embedded material. All tumors were classified by stage, histologic type, degree of differentiation and survival rates. In 4 cases, intestinal metaplasia cells in the adjacent mucosae were also microdissected. Six cases of moderate-severe gastric dysplasia were also added to the study. LOH was determined in 84% of the informative cases of GC, affecting both early and advanced stages of disease. Genomic instability was assessed in 5 cases, 3 of them associated with LOH. The only case of gastric cancer that did not show LOH or instability at 5q21 was a stage II, poorly differentiated intestinal carcinoma without evidence of recurrence after a 36 month follow-up period (the mean survival rate in our series was 28.3% at 36 months). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal metaplasias. Our data show that LOH at 5q21 is frequent in gastric cancer and is also present in intestinal metaplasia and dysplastic lesions. LOH at this locus is not a prognostic factor in GC in our study, due to the high incidence of LOH that we found.
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PMID:LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions. Prognostic implications. 918 90

We performed a detailed and comprehensive study of the involvement of tumor suppressor genes in human prostate cancer. We utilized primers flanking either the restriction fragment length polymorphism (RFLP) or variable number of tandem repeat [VNTR; microsatellite or simple repeat site (SRS)] polymorphic sites to polymerase chain reaction (PCR) amplify the genomic DNA and detect loss of heterozygosity of the target genes. Quantitative reverse transcription (RT)-PCR was performed to measure the mRNA expression levels and PCR/single strand conformational polymorphism (SSCP) and DNA sequencing carried out to detect mutation of the tumor suppressor genes. We found that multiple tumor suppressor genes (e.g., p53, DCC, APC, MCC, BRCA1, and WAF1/CIP1) were inactivated at different frequencies via various mechanisms [e.g., loss of heterozygosity (LOH), loss of expression (LOE), mutation, and inactivation by cellular binding protein]. Several important and novel findings are as following: LOH and LOE of the DCC gene, LOH, LOE, and possible mutation of the APC/MCC genes, LOH of the BRCA1 locus, and mutation of the WAF1/CIP1 gene. For p53 tumor suppressor gene alone, multiple inactivation mechanisms (i.e., LOH, LOE, mutation, and amplification of the cellular inactivating protein MDM2) were identified. A possible involvement of genomic instability or mutator phenotype in human prostate cancer was investigated by microsatellite typing using PCR. A high frequency of microsatellite instability was detected and the microsatellite instability found to correlate with advanced stage and poor differentiation of prostate cancer, suggesting that genes functioning in DNA mismatch repair or general stabilization of the genome may be involved in prostate cancer. The results obtained in this study suggested that multiple tumor suppressor genes (both known and unknown genes) may share the role in prostate cancer; a pattern which has been found in a number of human malignancies such as cancers of the esophagus, colon and breast. In fact, we performed deletion studies aimed at localizing potential tumor suppressor loci on various chromosomal regions. A number of chromosomal regions (i.e., 6p12-24 and 17q21) were found to potentially harbor unidentified tumor suppressor genes. Detailed deletion mapping has localized the potential tumor suppressor loci to a < 2 Mb region centromeric to the BRCA1 gene on chromosome 17q. In addition, we identified a number of novel mechanisms of tumor suppressor gene inactivation, in prostate cancer such as loss of mRNA expression of the DCC, APC, MCC and p53 gene, and mutator phenotype. And for the very first time, we identified somatic mutations of the WAF1/CIP1 gene in primary human malignancy-human prostate cancer. This finding provides the first evidence in primary tumor that the WAF1/CIP1 gene may be a tumor suppressor gene and may be involved in prostate cancer. We identified 12-lipoxygenase (12-LOX) as a potential prognostic marker for human prostate cancer. mRNA expression levels of the 12-LOX gene was measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and semi-quantitative in situ hybridization (ISH) in 122 pairs of matched normal and tumor tissues from prostate cancer patients. We found that 12-LOX expression levels were elevated in approximately half of the patients analyzed and the 12-LOX elevation correlates with advanced stage, poor differentiation, and surgical margin positivity. Our data suggest that 12-LOX may serve as a correlative marker for a more aggressive phenotype of prostate cancer and therefore for poor prognosis. We are currently refining our assays for possible clinical applicability. Since not all patients with loss of expression of the DCC gene showed LOH of the DCC locus, there must be other mechanism(s) responsible for loss of expression of the DCC gene. When we analyzed the relationship between DCC loss of expression and 12-LOX elevation in prostate cancer pati
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PMID:Involvement of the multiple tumor suppressor genes and 12-lipoxygenase in human prostate cancer. Therapeutic implications. 932 30

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

Pancreatic cancer is the fifth leading cause of cancer death in the United States, and despite improvements in the results of surgical treatment for this disease, little impact has been made upon overall mortality. New advances in treatment will depend upon improved adjuvant therapy, early diagnosis, and a better understanding of tumor biology. This article summarizes the results of molecular genetic studies in pancreatic cancer and their potential clinical significance. Familial predisposition to pancreatic cancer, cytogenic studies, DNA ploidy analysis, and examination of specific oncogenes and tumor suppressor genes are reviewed. The most frequent mutations detected have been in the K-ras oncogene, which occur in 80% of pancreatic cancers. These mutations do not correlate with tumor stage or survival, but can be useful in differentiating pancreatic exocrine from endocrine tumors and chronic pancreatitis. Mutations in the p53 gene occur in approximately 50% of tumors, and appear to be an independent prognostic factor for patient survival. Mutations in the CDKN2 gene are frequently seen in sporadic pancreatic cancers, and have been implicated in cases of familial pancreatic cancer. The significance of mutations in APC, MCC, DCC, c-erbB-2, RB-1, and mismatch repair genes in the genesis of pancreatic cancer is less clear.
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PMID:The molecular genetics of pancreatic cancer. 936 57

Previously, we have reported that the inactivation of putative tumor-suppressor gene(s) on chromosome 5q21-22 may play an important role in the progression of lung cancer. Here, we describe the establishment of a yeast artificial chromosome (YAC) contig that spans 8-10 Mb at the 5q21-22 region. Six cosmid contigs have also been established in this YAC contig. About 35 exon-like fragments have been detected by exon-amplification, direct screening, cross-species hybridization, and searches of a database. Thus far, 14 cDNAs have been isolated, and two of them coincide with known genes, viz., cysteine dioxygenase I and geranylgeranyltransferase I. The other 12 cDNAs are considered to be novel genes. Two of these novel cDNA show partial homology to known genes, viz., semaphorin CD100 and the 28S rRNA gene. In addition, four known genes, including APC (adenomatous polyposis coli), MCC (mutated in colorectal cancer), proto-oncogene tyrosine kinase FER, and genomic imprinted gene U2AF1-RS1, have also been mapped in this contig. This large contig and expression map should prove crucial in the identification of susceptibility gene(s) related to the progression of lung cancer.
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PMID:Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer. 949 Mar 1

Familial juvenile polyposis (FJP) is a hamartomatouspolyposis syndrome in which affected family members develop upper and lower gastrointestinal juvenile polyps and are at increased risk for gastrointestinal cancer. A genetic locus for FJP has not yet been identified by linkage; therefore, the objective of this study was to perform a focused genome screen in a large family segregating FJP. No evidence for linkage was found with markers near MSH2, MLH1, MCC, APC, HMPS, CDKN2A, JP1, PTEN, KRAS2, TP53, or LKB1. Linkage to FJP was established with several markers from chromosome 18q21.1. The maximum LOD score was 5.00, with marker D18S1099 (recombination fraction of .001). Analysis of critical recombinants places the FJP gene in an 11.9-cM interval bounded by D18S1118 and D18S487, a region that also contains the tumor-suppressor genes DCC and DPC4. These data demonstrate localization of a gene for FJP to chromosome 18q21.1 by linkage, and they raise the possibility that either DCC or DPC4 could be responsible for FJP.
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PMID:A gene for familial juvenile polyposis maps to chromosome 18q21.1. 954 10

To evaluate the role of APC, MCC and DCC genes in the development and progression of colorectal cancers, loss of heterozygosity (LOH) at these genetic loci was investigated in 41 surgically resected specimens of colorectal cancer by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. LOH at APC or/and MCC was detected in 38.9% (14/38) of the informative cases; at the APC in 28.0% (7/25) and at MCC locus in 36.4% (8/22). LOH at DCC genetic locus was detected in 55.3% (21/38) of the informative cases. LOH rates DCC gene in the cancer specimens with lymphnode metastasis (80.0%) and in Dukes' stage III and IV (71.4%) were significantly higher than that in specimens without lymphnode metastasis (39.1%) and in Dukes' stage I and II (35.3%) (P < 0.05). Our results suggest that LOH at APC/MCC and DCC is the common genetic alterations in colorectal cancer and DCC genetic LOH assay may be useful in predicting the prognosis of patients with colorectal cancer.
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PMID:[A study on the loss of heterozygosity at the APC/MCC and DCC genetic loci in colorectal cancers]. 959 12


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