Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve well-differentiated villoglandular adenocarcinomas (WDVAs) of the uterine cervix were retrospectively analyzed for the presence and specific genotype of human papillomavirus (HPV), tumor suppressor loss (p53, MCC, APC, BRCA1), cancer gene mutation (K-ras-2, exons 1 and 2, p53 exons 5 to 8), and oncogene amplification (c-erbB-2/HER-2/neu, int-2). Tissue for genetic evaluation was obtained by microdissection, using 4-micron-thick histology sections of archival, formalin-fixed, paraffin-embedded specimens. Genotyping involved nucleic acid amplification and DNA sequencing with gene-specific oligonucleotides and L1 region consensus primers for common strains of HPV. Point mutation and HPV strain determination were accomplished by DNA sequence analysis. Tumor suppressor gene loss and oncogene amplification were performed by allelic imbalance analysis in informative subjects based on DNA sequence and microsatellite-length polymorphisms. HPV was present in all tumors and consisted of type 16 (n = 5, 42%) and type 18 (n = 7, 58%) strains, which have been closely associated with cervical neoplasia. K-ras-2 and p53 genes did not manifest point mutational damage. There was no evidence of oncogene amplification or tumor suppressor gene loss. The presence of HPV in all 12 tumors supports the role of HPV infection in the molecular pathogenesis of this uncommon neoplasm. The absence of associated oncogene or tumor suppressor gene damage is consistent with indolent biological behavior and the favorable prognosis of this unusual tumor.
 ...
PMID:Well-differentiated villoglandular adenocarcinoma of the uterine cervix: oncogene/tumor suppressor gene alterations and human papillomavirus genotyping. 1078 6

Activation of the beta-catenin/T cell factor-mediated transcription pathway through mutations of the APC or beta-catenin gene is suggested to play an important role in colon carcinogenesis and there is great interest in the target genes. We have described the frequent mutation and an altered cellular localization of beta-catenin in rat colon adenocarcinomas induced by azoxymethane (AOM), along with up-regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. In the present study, the relation between beta-catenin alteration and expression of iNOS and COX-2 in AOM-induced rat colon carcinogenesis was examined in hyperplastic and dysplastic type aberrant crypt, adenoma and adenocarcinoma samples. K-ras gene mutations were also investigated. Mutation analysis by the PCR-single strand conformation polymorphism method and direct sequencing demonstrated the beta-catenin gene to be mutated in two of three dysplastic aberrant crypt foci (ACF), two of six adenomas and 20 of 26 adenocarcinomas, while K-ras was mutated in seven of 10 hyperplastic ACF and seven of 26 adenocarcinomas. Immunohistochemical staining showed an alteration in cellular localization of beta-catenin in all dysplastic ACF, adenomas and adenocarcinomas examined. iNOS expression was also observed in all but one of the lesions in which beta-catenin alterations were observed. Neither iNOS expression nor beta-catenin alterations were observed in any hyperplastic ACF. COX-2 expression in stromal elements was found even in normal colon mucosa and increased in adenomas and adenocarcinomas, while epithelial cells were only positive in large adenocarcinomas. These results show that beta-catenin alterations may be related to induction of iNOS expression, these being early events in AOM-induced colon tumorigenesis which may play important roles in causing dysplastic changes.
 ...
PMID:Altered expression of beta-catenin, inducible nitric oxide synthase and cyclooxygenase-2 in azoxymethane-induced rat colon carcinogenesis. 1087 9

To elucidate the relationship between genetic alterations and cellular phenotypes in differentiated-type carcinomas and precancerous lesions of the stomach, mutations of p53, APC and K-ras genes were examined, as well as microsatellite instability (MSI), in 52 tumours of the stomach. Tumours were selected with the following phenotypical features, using mucin histochemical and immunohistochemical analyses, in addition to their morphological features: (1) tumours with an extremely well-preserved gastric foveolar phenotype (foveolar-type); (2) tumours with an extremely well-preserved complete-type intestinal metaplastic phenotype (CIM-type); and (3) ordinary tumours without extreme phenotypes (ordinary-type). MSI occurred in 45% of foveolar-type, 24% of ordinary-type, and 0% of CIM-type tumours. p53 gene alterations occurred in 5% of foveolar-type, 18% of ordinary-type, and 31% of CIM-type. APC gene alterations were detected in 9% of foveolar-type, 6% of ordinary-type, and 0% of CIM-type. No K-ras gene mutation was detected in any of the three types. These results indicate that the genetic pathways are quite different among the phenotypes of tumours of the stomach. The 'mutator pathway', characterized by MSI, plays an important role in the tumourigenesis of foveolar-type, but not CIM-type tumours. The 'suppressor pathway', represented by p53 alteration, could participate in the tumourigenesis of the CIM-type, but is rare in foveolar-type tumours.
 ...
PMID:Cellular phenotypes of differentiated-type adenocarcinomas and precancerous lesions of the stomach are dependent on the genetic pathways. 1174 2

Colon carcinogenesis induced in rats by azoxymethane (AOM) is a useful experimental model as it mimics the human adenoma-carcinoma sequence and allows the study of dietary variation and of the effects of chemopreventive substances. Alterations of specific oncogenes and tumor suppressor genes (APC and K-ras) play roles at different stages of this carcinogenesis process. Recently, it has been suggested that genomic instability is the necessary step for the generation of multiple mutations underlying the occurrence of cancer. We studied the frequency of K-ras and microsatellite instability (MSI) in 30 colorectal tumors induced by AOM (30 mg/kg) in F344 rats. We also used the random amplified polymorphic DNA (RAPD) method to identify genomic alterations in chemically induced aberrant crypt foci (ACF), adenomas and adenocarcinomas. K-ras mutations were identified in 16.7% of the cases (5/30; 9% in adenomas and 37.5% in adenocarcinomas) and MSI in 20% (6/30) of the tumors (only one sample exhibited instability at more than one locus). Of 21 primers used for the RAPD assay, six were very informative. All the analyzed tumors (16/16) showed at least one RAPD profile with lost or additional bands compared with the normal mucosa. A lower level of genomic alteration was present in the ACF analyzed (7/10). In conclusion, K-ras and MSI are not often involved in the AOM carcinogenesis in the rat, whereas extensive genomic instability is always present and can be detected using the RAPD analysis.
 ...
PMID:Detection of somatic DNA alterations in azoxymethane-induced F344 rat colon tumors by random amplified polymorphic DNA analysis. 1096 8

The multistep genetic model of colorectal carcinogenesis is based on the concept of the adenoma-carcinoma sequence. The adenoma-carcinoma sequence theory has been generally accepted for polypoid early colorectal cancers (ECCs). On the other hand, an increasing number of nonpolypoid (superficial) ECC have been reported. Nonpolypoid (superficial) ECCs show distinct characteristics histologically and genetically, and some claim these lesions may develop by de novo type carcinogenesis. In fact, clinicopathologic studies have shown that most nonpolypoid (superficial) cancers have no adenomatous lesions in the surrounding area. Genetic analyses have also revealed that nonpolypoid (superficial) ECCs show a pattern of genetic alterations different from that of polypoid ECCs. The K-ras mutation rate is lower in nonpolypoid (superficial) ECCs than in polypoid ECCs, but there is no significant difference in the p53 mutation rate between two types of tumor. During the development of ECCs, the K-ras gene seems to determine the macroscopic configuration: whether polypoid or nonpolypoid (superficial). These results suggest that nonpolypoid (superficial) ECCs originate from a pathway different from the conventional genetic pathway that follows the adenoma-carcinoma sequence. However, this does not mean that this new pathway is following de novo type carcinogenesis, because there is a possibility that nonpolypoid (superficial) adenomas, or so-called flat adenomas, develop into nonpolypoid (superficial) ECCs following the adenoma-carcinoma sequence. At the present time, there is still not enough evidence to conclude whether nonpolypoid (superficial) ECC is derived from de novo carcinogenesis or the conventional adenoma-carcinoma sequence. Further analysis, especially concerning APC gene mutation in ECCs, is essential to elucidate the carcinogenesis of nonpolypoid (superficial) ECCs.
 ...
PMID:Colorectal carcinogenesis based on molecular biology of early colorectal cancer, with special reference to nonpolypoid (superficial) lesions. 1103 87

We described two patients (brother and sister) with familial adenomatous polyposis of the colon. It is an inherited disease with autosomal dominant pattern of inheritance. The incidence is 1:8.000, with usual onset of polyps development late in the first decade of life or during adolescence, and malignant alteration up to the fourth decade of life. APC gene located on long arm of chromosome 5 is responsible for occurrence of the disease that presents with onset of multiple adenomatous polyps in the colon (from some of them to 1000). The treatment includes chemoprevention by sulindac or aspirin that prevents or reverse process of carcinogenesis. Surgical approach is preventive colectomy up to 20 (25) years of life. APC gene mutation (deletion at codon 1309-1311) was proven by DNA analysis from blood and polyp in both patients. There was no evidence of mutations of genes p53 and K-ras. Preventive colectomy is planned as soon as possible.
 ...
PMID:[Familial adenomatous colonic polyposis]. 1104 May 35

Peutz-Jeghers syndrome (PJS) is characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous melanin deposition, and increased risk of cancer, mainly in the gastrointestinal tract. We examined mutations of the LKB1, beta-catenin, APC, K-ras, and p53 genes in 27 gastrointestinal hamartomatous polyps from 10 patients in nine PJS families. Of these hamartomatous polyps, one intestinal polyp had an adenomatous lesion, and one gastric polyp contained adenomatous and carcinomatous lesions. Germ-line mutations of the LKB1 gene were detected in six PJS families. Somatic mutations of the LKB1 gene were found in 5 polyps, whereas loss of heterozygosity (LOH) at the LKB1 locus at 19p was seen in 14 other polyps. In adenomatous lesions microdissected from hamartomatous polyps, both beta-catenin mutation and 19p LOH were detected. Furthermore, a carcinomatous lesion in a gastric hamartomatous polyp was found to contain a mutation of the p53 gene and LOH at the p53 locus in addition to LOH at the LKB1 locus and a beta-catenin mutation. K-ras mutations were detected in a few polyps, whereas no APC mutation or 5q LOH was detected in hamartomatous polyps. These results suggest that gastrointestinal hamartomatous polyps in PJS patients develop through inactivation of the LKB1 gene by germ-line mutation plus somatic mutation or LOH of the unaffected LKB1 allele, and that additional mutations of the beta-catenin gene and p53 gene convert hamartomatous polyps into adenomatous and carcinomatous lesions.
 ...
PMID:Somatic mutations of LKB1 and beta-catenin genes in gastrointestinal polyps from patients with Peutz-Jeghers syndrome. 1110 90

We analyzed K-ras and p53 mutations, microsatellite instability (MSI), and loss of heterozygosity (LOH) using the polymerase chain reaction (PCR) methods, as well as p53 expression and the Ki-67 labeling index (LI) using immunohistochemistry in 10 duodenal and 10 jejunal/ileal carcinomas. K-ras mutations were detected in two duodenal (20%) and three jejunal/ileal (30%) carcinomas and p53 mutations in one (10%) and three (30%), respectively. LOH of 17p was detected in two duodenal (20%) and two jejunal/ileal (20%) carcinomas and p53 expression in four duodenal (40%) and four jejunal/ileal (40%). One duodenal (10%) and two jejunal/ileal (20%) carcinomas demonstrated MSI. LOH of APC was detected in three jejunal/ileal (30%), but none of the duodenal carcinomas. The Ki-67 LI was 44% in duodenal and 52.6% in jejunal/ileal carcinomas. A subset of small intestinal carcinomas showed involvement of K-ras and p53 mutations, LOH of APC, and MSI. A difference was also apparent for LOH of APC between duodenal and jejunal/ileal carcinomas.
 ...
PMID:Combination analysis of genetic alterations and cell proliferation in small intestinal carcinomas. 1111 78

Genetic and epigenetic alterations of multiple cancer-related genes and molecules are implicated in the development and progression of human gastric carcinomas. Reactivation of telomerase, inactivation of p53 tumor suppressor gene, overexpression of cyclin E, and reduced expression of p27 KIP1 by disorganized degradation in proteasome are common events of both well-differentiated and poorly differentiated gastric adenocarcinomas. Inactivation of hMLH1 mismatch repair gene by CpG hypermethylation resulting in microsatellite instability, amplification of c-erbB2 oncogene, inactivation of APC tumor suppressor gene, and K-ras mutations are preferentially associated with well-differentiated gastric cancer. Conversely, reduction or loss of E-cadherin and catenins by both mutation and CpG hypermethylation and K-sam and c-met oncogene amplification are necessary for the development and progression of poorly differentiated or scirrhous gastric carcinomas. Interaction between cancer cells expressing c-met and hepatocyte growth factor from stromal cells is implicated in morphogenesis of gastric cancer.
 ...
PMID:Genetic and epigenetic changes in stomach cancer. 1124 97

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.
 ...
PMID:A double germline mutations in the APC and p53 genes. 1126 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>