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)

Seventy malignant, premalignant and histologically normal biopsies from 7 oesophagogastrectomy specimens of adenocarcinomas of the lower oesophagus and gastroesophageal junction were analysed for loss of heterozygosity (LOH) at 9 known or putative gene loci. LOH was detected in 20 of 27 (74%) malignant biopsies, 4 of 7 (57%) biopsies of dysplasia, 2 of 12 (25%) biopsies of histologically normal oesophagus adjacent to adenocarcinoma, and in 2 of 14 (14%) biopsies of histologically normal stomach adjacent to adenocarcinoma. LOH at the VHL, APC, CDKN2 and DCC tumour suppressor and MSH3 mismatch repair gene loci can be detected in histologically normal tissue and in adjacent adenocarcinoma, and are potential markers of early neoplastic progression.
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PMID:Histological and molecular mapping of adenocarcinoma of the oesophagus and gastroesophageal junction: loss of heterozygosity occurs in histologically normal epithelium in the oesophagus and stomach. 1076 62

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver in Japan. Despite progress in operative techniques and adjuvant therapy, the prognosis of ICC remains very poor. Therefore, it is important to investigate the mechanism of carcinogenesis and progression of ICC. We screened allelic losses at 6 loci, including that of novel tumor-suppressor gene FEZ1 on chromosome 8p, and at 5 microsatellite loci to define the association with tumor-suppressor genes (HNPCC, APC, RB1, p53, DCC) in tumors from 18 unrelated ICC patients by PCR-loss of heterozygosity (LOH) assay and correlated the alterations with clinicopathological parameters. As a result, 61.1% (11 of 18) of patients showed LOH at 1 of the loci at least, and microsatellite instability was observed in 16.7% (3 of 18). At locus D8S258, relatively frequent LOH was detected (17.6%) compared with other loci on chromosome 8p. Among the other 5 chromosomal arms tested, the highest frequency of LOH (23.5%) was observed at D17S153. Fifty percent of cases with the mass-forming + periductal infiltrating type were frequently detected by LOH at D8S258 compared to cases of the mass-forming or intraductal growth type. In conclusion, we show that 1 putative tumor-suppressor gene on 8p22 may relate to progression of ICC and suggest that the p53 tumor-suppressor gene may be associated with carcinogenesis of ICC.
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PMID:Allelic loss in human intrahepatic cholangiocarcinoma: correlation between chromosome 8p22 and tumor progression. 1100 73

Although the genetic basis for gallbladder carcinogenesis has not been clarified, considerable evidence has shown that genetic alterations play an important role in the development and progression of human cancers. In this study, we analyzed 30 gallbladder carcinomas to investigate the role of genetic alterations in their tumorigenesis, and to study correlations with their clinicopathological features. Tissue samples were obtained from 30 patients with gallbladder carcinoma (11 men and 19 women; mean age, 62 years; age range, 38-80 years). Genomic DNAs were extracted from fresh tumor tissue. We examined loss of heterozygosity (LOH) in the p53, APC, DCC, RB, and NM23-H1 gene regions by polymerase chain reaction (PCR)-LOH assay using an automated fluorescent DNA sequencer employing four microsatellite markers (p53, APC, DCC, NM23-H1). Five additional microsatellite markers were used for the determination of microsatellite instability (MSI). LOH was found at p53 in 9 of 15 informative cases (60%), at DCC in 10 of 22 (45%), at APC in 5 of 15 (33%), at RB in 1 of 8 (13%), and at NM23-H1 in 1 of 15 (7%). MSI was observed in 5 of 30 cases (17%) in at least one chromosomal loci of these nine microsatellite markers. None of the patients with MSI-positive tumors showed lymph node metastasis, and there was an inverse correlation between MSI and the presence of LOH in gallbladder carcinoma. These results suggest that there are two independent genetic pathways in gallbladder carcinogenesis; that is, an MSI pathway and an LOH pathway.
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PMID:Microsatellite instability in gallbladder carcinoma: two independent genetic pathways of gallbladder carcinogenesis. 1106 28

Cell growth is under the control of a variety of positive and negative signals. An imbalance of such signals results in deregulation of cell behavior. Recessive oncogenes or tumor suppressor genes, opposite to dominant oncogenes, encode important cellular proteins which could function as negative regulators of the cell cycle, i.e., cell cycle brakes. Inactivation of recessive oncogenes, by allelic deletion, loss of expression, mutation, or functional inactivation by interacting with oncogene products of DNA tumor viruses or with amplified cellular binding proteins, will lead to uncontrolled cell growth or tumor formation. Besides the classic suppressor genes such as the p53 and RB, a growing number of novel tumor suppressor genes have been identified in recent years. While some tumor suppressor genes have been found to be important for the development of a large number of human malignancies (e.g., the p53 gene), others are more tumor type-specific (e.g., the NF-1 gene). Many human cancer types showed abnormalities of multiple tumor suppressor genes, offering strong support to the concept that tumorigenesis and progression result from an accumulation of multiple genetic alterations. In this review, we will begin with an overview (gene, transcript, protein and mechanisms of action) of the tumor suppressor genes (the RB, p53, DCC, APC, MCC, WT1, VHL, MST1, and BRCA1 genes) identified to date and then discuss the specific involvement of tumor suppressor genes in human malignancies including prostate cancer. Various chromosomal regions which potentially may contain tumor suppressor genes also will be reviewed.
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PMID:Recessive oncogenes: current status. 1117 62

Adenocarcinoma of the gastroesophageal junction is rapidly rising in incidence. It has been proposed that these tumors be classified as three different types: distal esophageal (AEG I), cardia (AEG II), and subcardia (AEG III). Using comparative genomic hybridization (CGH) analysis, one recent study reported that the 14q chromosomal arm showed a significantly higher rate of deletion in esophageal than in cardia adenocarcinoma. Using a microsatellite analysis technique, we analyzed this area and regions in the vicinity of the APC, DCC, and p53 genes. Tumor and normal tissues were microdissected from 54 cases (27 AEG I and 27 AEG III). DNA was extracted and then amplified using seven fluorescent-labeled microsatellite markers, one pair each on 5q, 18q, and 17p and four on 14q. The results were analyzed for loss of heterozygosity (LOH) and microsatellite instability (MSI). LOH varied from 20% to 30% at each locus except for the 17p locus, where it was slightly above 50% in both groups. No significant differences in LOH or MSI were found between the esophageal and gastric tumors, including the 14q chromosomal arm. These results fail to confirm the finding that abnormalities on the 14q chromosomal arm distinguish between distal esophageal and proximal gastric tumors.
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PMID:Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach. 1119 71

In order to determine the molecular genetic alterations associated with tumor invasion, Barrett's adenocarcinoma and its non-invasive precursor lesions were investigated by comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), and loss of heterozygosity (LOH). Along the metaplasia-dysplasia-carcinoma sequence in Barrett's adenocarcinoma gains on 7q, 8q, 20q, 2p, 10q and 17q, and losses on Y, 4q, 5q, 9p 18q and 14q became steadily more frequent. FISH demonstrated increasing DNA copy of numbers of c-erbB-2, 20q13.2 (AIB), c-myc and cyclin D1 during the development of Barrett's adenocarcinoma, and LOH confirmed DNA losses on 5q21 (APC) and 18q (DCC). Some of the chromosomal changes of the non-invasive precursor lesions were significantly different from the alterations detected in invasive carcinoma. Although molecular pathology may be used as diagnostic adjunct in future, the histopathological determination of invasion remains the most important diagnostic criterion of malignancy in Barrett's adenocarcinoma.
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PMID:[Morphology and biology of invasion with Barret's carcinoma as an example]. 1121 50

Germline mutation in the APC gene is required for the initiation of the development of familial adenomatous polyposis (FAP). According to Fearon and Vogelstein model, further somatic mutations in the K-ras oncogene, DCC gene and p53 tumor suppressor gene are prerequisite for development of colon carcinoma. We have found that the germline mutations in the DNA isolated from lymphocytes of an 18 years old girl with extraordinary expressive phenotype in codons 1060-1061 of the APC gene result in truncation of the APC protein. The mutation in codons 12 and 13 of the K-ras oncogene was not detected, but another germline mutation was found in codon 210 of the p53 gene. Furthermore, no one of these germline mutations was detected in the DNA of peripheral blood lymphocytes of the patient's 21 years old healthy sister. Until now, there has been no evidence about the expressive phenotype due to mutation in codons 1060-1061 of the APC gene; the role of germline missense mutation in codon 210 of the p53 gene in the FAP malignant process remains to be elucidated too. The effect of the combination of germline mutation in two different tumor suppressor genes in the progress of disease is discussed.
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PMID:A double germline mutations in the APC and p53 genes. 1126 56

Colorectal adenomas can be morphologically classified as exophytic or flat. Polypoid cancers and cancers arising de novo (ie., without any adenomatous component) might be the results of genetic progression from exophytic and flat adenomas, respectively. In this study, we examined 94 morphologically distinct neoplastic specimens for mutations in K-RAS and analyzed 10 microsatellite loci tightly linked to the tumor suppressor genes APC, p53, DCC/SMAD4, hMSH2, and hMLH1. K-RAS mutations were significantly associated with exophytic adenomas [11 of 21 (52%)] compared to flat adenomas [2 of 13(15%), P < 0.03] and polypoid cancers [17 of 25 (68%)] compared to cancers arising de novo [7 of 25 (28%), P < 0.01]. Two polypoid cancer cases demonstrated three and four different K-RAS mutations, respectively, suggesting multiple areas of clonal expansion. Cancers arising de novo were significantly associated with loss of heterozygosity (LOH) at chromosome 3p compared to pol ypoid cancers [6 of 18(33%) versus 1 of 20(5%), P < 0.03], whereas the prevalence of LOH at chromosomes 2p, 5q, 17p, and 18q and microsatellite instability were not different between the groups. For all cancers, LOH at chromosomes 17p and 18q occurred in 47 and 51%, respectively. However, LOH at 17p and 18q occurred in 0 and 16% of benign lesions, respectively, suggesting their role in malignant transformation. There was no difference in LOH at chromosomes 17p and 18q between exophytic and flat lesions. These findings suggest that (a) mutant K-RAS is associated with the exophytic growth of colonic neoplasms, and that (b) some colorectal cancers arising de novo lose chromosome 3p during their evolution, which is not seen in polypoid cancers. Half of all cancers lose chromosomes 17p and 18q at or near the malignant transition of benign lesions as reported previously, irrespective of morphology. There may be more than one genetic avenue for colorectal cancer formation, and this correlates with the morphological characteristics.
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PMID:Genetic pathways in the evolution of morphologically distinct colorectal neoplasms. 1128 47

Colorectal carcinogenesis is widely accepted as one of the best-characterized examples of stepwise progression. The existing colorectal carcinogenesis model assumes genetic homogeneity of individual tumors for the main known genetic alterations: K-ras and p53 genes point mutations and loss of heterozygosity (LOH) of chromosome 5q and 18q. The object of the present study was to demonstrate the existence of an intratumor genetic heterogeneity in advanced sporadic colorectal carcinoma for these genetic alterations. Using improved tissue microdissection and DNA extraction, for each tumor, amplifiable DNA was obtained from 15 to 20 areas, of which 1 to 2 concerned lymph node metastases (LNM). This study revealed that 10 of 15 (67%) analyzed tumors were heterogeneous for at least 1 genetic alteration, with between 2 and 6 genotypically different clones detected per tumor. No correlation was observed between the genotype of these subclones and histological differentiation or invasive propensity. Intratumor heterogeneity was more frequently observed for LOH than for point mutations, 67% and 58% for LOH at APC and DCC locus, and 20% for mutation of either the K-ras or p53 gene. In 5 of the 9 (56%) heterogeneous cases with available LNM, the genotype observed in the LNM was different from that of the main clone in the primary tumor, and moreover, 2 of the LNM displayed a genotype undetected in the primary tumor. In conclusion, intratumor genetic heterogeneity was demonstrated in advanced sporadic colorectal carcinoma and was represented as topographically distinct genotypic subclones. Taking into account such a significant genetic heterogeneity of colorectal tumors, the use of genetic markers for prognosis management should be reconsidered.
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PMID:Intratumor genetic heterogeneity in advanced human colorectal adenocarcinoma. 1143 98

The deficiencies of nucleotide excision repair (NER) factors are involved in rare genetic diseases such as xeroderma pigmentosum (XP) with increased risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (LOH) analysis, using the microdissected tissues, for the XPA, XPB, XPC, XPD, XPE, XPF, XPG and the transcription-coupled repair factor, Cockayne syndrome B (CSB) revealed that NER factors were abnormal in 30.0% (3/10 cases) of oral squamous cell carcinomas. Furthermore, 10.0% of oral carcinomas exhibited LOH for NER factors without LOH for tumor suppressor genes such as p53, FHIT, APC, BRCA1, BRCA2 and DCC. These observations raise the possibility that alterations of NER factors may be involved in carcinogenesis in human oral squamous cell carcinoma.
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PMID:Loss of heterozygosity of nucleotide excision repair factors in sporadic oral squamous cell carcinoma using microdissected tissue. 1149 30


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