Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A putative tumor suppressor gene, p16 (MST1; multiple tumor suppressor 1/CDK4I; cyclin-dependent kinase 4 inhibitor), was isolated and mapped on the short arm of chromosome 9 (9p). The significance of p16 mutations in gastric tumorigenesis was examined by assessing p16 mutations as well as loss of heterozygosity (LOH) on 9p in 13 gastric adenomas and 45 adenocarcinomas. LOH on 9p (IFNA; alpha-interferon locus) was detected in 22% (5/23 informative cases) of differentiated adenocarcinomas, 10% (1/10) of undifferentiated carcinomas and none (0/6) of the adenomas. Although we found a sequence polymorphism at the second position of codon 99 (CGC/CAC) of the p16 in one gastric adenoma patient, no somatic mutations were detected in any of the gastric adenomas or adenocarcinomas. These results suggest that p16 mutations probably do not contribute to gastric tumorigenesis. However, these data suggest that another tumor suppressor gene on 9p (near the IFNA locus) may contribute to the progression of differentiated adenocarcinoma of the stomach.
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PMID:Loss of heterozygosity on the short arm of chromosome 9 without p16 gene mutation in gastric carcinomas. 777 54

The incidence of multiple tumours in renal cancer ranges between 1 and 30%. In these cases, it becomes very difficult to differentiate between adenoma and carcinoma just by using conventional methods, particularly in borderline cases. We carried out primary cultures and subsequent cytogenetic studies in 2 patients with multiple renal cancer. Clonal numerical changes in the first case were: 3, 7, 16 and 17 trisomies, chromosome loss; and structural changes, del(1) (p34), del(2) (p16, p22). In the second case, clonal numerical changes were 7 trisomy and tetrasomy and loss of the Y chromosome. Both tumours were cytogenetically characterized as papillary renal tumours. The diagnostic approaches are discussed and the prognosis possibilities evaluated, using this method to evaluate them in multiple renal tumours.
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PMID:[Cytogenetic characteristics and of primary culture in multiple renal tumors]. 836 10

pRB, the retinoblastoma tumor suppressor gene product, regulates the cell cycle at G1/S transition negatively. Many cell cycle regulators modulate pRB function through its phosphorylation status. G1 cyclins (cyclin D, E)/cyclin-dependent kinases (cdk2, 4) inactivates pRB through its phosphorylation, while p21 (WAF1) and p16 inhibit cdks. In several kinds of cancer, Rb gene alteration or functional inactivation of pRB has been reported. In esophageal cancer, loss of heterozygosity of Rb gene and cyclin D gene amplification were frequently detected. But in gastric and colorectal cancer, Rb gene loss or deletion has been shown to be rare. In this study we investigated the expression of pRB, G1 cyclins, cdks and cdk-inhibitors in adenoma-carcinoma sequence of colorectum. And we compared the phosphorylation status of pRB in colorectal normal mucosa and cancer tissue. In adenoma only cyclin D and E were overexpressed but not cdks. In cancer in adenoma pRB and cdk2 were overexpressed with high frequency, and cdk4 overexpression was detected in advanced cancer. p16 overexpression was detected in almost all cancers, but in contrast p21 overexpression was rare event. Comparative study showed that pRB-positive cancer cells also expressed both cdc2/cdk2 and cyclin E. Densitometric analysis revealed that in advanced cancer pRB was hyperphosphorylated compared with normal mucosa. These results indicate that overexpression of cyclin D/cdk4 and cyclin E/cdk2 would phosphorylate pRB, and insufficient expression of p21 may accelerate pRB inactivation.
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PMID:[RB gene expression in gastrointestinal tract]. 892 Jun 58

G1/S transition of cell cycle is regulated by G1 cyclins/cyclin-dependent kinases (CDKs) and their inhibitors. Cyclin D/CDK4 complex phosphorylates retinoblastoma gene product and p16 inhibits CDK4 in competition with cyclin D. Aberrant expression of these proteins may deregulate cell proliferation and moreover may lead to tumor formation and progression. In this study we examined the expression of cyclin D, CDK4 and p16 in adenoma-carcinoma sequence of colorectum. Immunohistochemical staining revealed that cyclin D was overexpressed in 55 of 66 (83%) adenomas, 8 of 8 (100%) carcinomas in adenoma (CIAs), 26 of 45 (58%) advanced carcinomas and even in hyperplastic mucosa. CDK4 was overexpressed in 0 of 52 (0%) adenomas, 0 of 14 (0%) CIAs and 39 of 45 (87%) advanced carcinomas, but not in hyperplastic mucosa. p16 was overexpressed in only 5 of 52 (10%) adenomas, 10 of 14 (71%) CIA and 59 of 60 (98%) advanced carcinomas, but not in hyperplastic mucosa. And comparative study of CDK4 and p16 showed that CDK4-positive cancer cells also expressed p16. Western blot analysis also revealed that primary regions of advanced colorectal cancer tissues showed 4.61, 3.30, 1.65 and 8.03-fold overexpression on the average in cyclin D1, cyclin D2, CDK4 and p16 respectively. These results indicate that both cyclin D and CDK4 may contribute to phosphorylation of pRB. p16 overexpression would be induced as a brake at G1/S transition through pRB phosphorylation by CDK4 overexpression in advanced colorectal carcinomas.
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PMID:[Cyclin D, CDK4 and p16 expression in colorectal cancer]. 892 Jun 73

The molecular pathway of autonomous growth of the parathyroid glands in uremic patients is poorly understood. We have analyzed 71 parathyroid lesions from 24 patients with refractory hyperparathyroidism for allelic loss at chromosomes 1, 3, 6, 9, 11, 12, 13, 15, and 17 and at the X chromosome. Microsatellite analysis was performed using 24 highly polymorphic markers. Deletions at chromosomes 1, 3, 6, 11, 12, and 13 and at the X chromosome were detected in only 10 of 67 nodules (15%). No allelic loss of the p16 and p53 tumor suppressor genes or the extracellular calcium receptor gene was found. The X-chromosome inactivation assay revealed a monoclonal pattern in 58% of hyperplastic nodules in females. Our results indicate monoclonal growth in the majority of hyperplastic nodules and suggest that some of these lesions might be considered precursors for adenoma development.
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PMID:Genetic abnormalities in parathyroid nodules of uremic patients. 951 73

Pleomorphic adenoma of the lung is a rare neoplasm. Here we describe the first report on oncogenes and tumor suppressor genes in metastasizing pleomorphic adenoma of the lung. A 48-year-old Japanese woman presented with metastasizing pleomorphic adenoma in which both the primary lung tumor and metastatic lesions were composed of benign pleomorphic structures. The mechanism of the metastatic potential was examined by analyzing known oncogenes and tumor suppressor genes by DNA blot analysis and immunohistochemistry. No rearrangements amplifications or overexpressions of oncogenes, bcl-2, c-erbB-2, c-myc, L-myc, N-myc, Ha-ras and Ki-ras were found. In addition, immunohistochemical studies showed no aberrance in expressions of the tumor suppressor gene products, RB, p16 and p53 in the tumor. Some unknown mechanism(s) seems to be responsible for the aggressiveness of this metastasizing pleomorphic adenoma. This mechanism must be elucidated by studies on further case of this rare tumor.
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PMID:A case of pleomorphic adenoma of the lung with multiple distant metastases--observations on its oncogene and tumor suppressor gene expression. 967 59

Loss of heterozygosity (LOH) of the MTS1 (p16) tumor suppressor gene has been reported to occur frequently in thyroid cancer cell lines. In order to determine the frequency of LOH for these multiple tumor suppressor genes, we used microsatellite markers IFNA and D9S171 to perform differential quantitative polymerase chain reaction. Tumor DNA was isolated from native sections of tumor tissue. Control DNA was isolated from blood. PCR products were separated on 6% polyacrylamide sequencing gels and quantified according to peak height and area. Analysis was informative in 70% of cases for both markers, and in 88% for at least one out of both. LOH was found in 3 out of 35 informative patients (8.6%) with papillary thyroid cancer, in 1 out of 7 patients with follicular thyroid cancer (14.2%), and in 0 out of 18 medullary cancers (0%). No LOH was found in 11 informative patients with multinodular goitre, 7 with follicular adenoma, 4 with Graves' disease, and 6 with other thyroid disease. 75% of LOH was found in T1 and T2 stages, it was not more frequent in patients with lymphonodular metastasis. The low frequency of LOH in these types of thyroid cancer argues against a role of loss of heterozygosity at the MTS 1 and 2 gene locus in the development of differentiated thyroid neoplasia.
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PMID:Rare loss of heterozygosity of the MTS1 and MTS2 tumor suppressor genes in differentiated human thyroid cancer. 980 21

DNA methylation of promoter-associated CpG islands may function as an alternate mechanism of silencing tumor suppressor genes in multiple neoplasias including colorectal cancer. De novo methylation of genes appears to be an early and frequent event in most neoplasias. For the ER and IGF2 genes, we have previously shown that methylation actually begins in the normal colon mucosa as an age-related event and progresses to hypermethylation in cancer. In this study, we have determined the frequency of age-related methylation in normal colonic mucosa among the genes hypermethylated in colorectal cancer. We studied six genes, including N33, MYOD, p16, HIC-1, THBS1, and CALCA. The N33 gene showed partial methylation in normal colon mucosa, which was age-related (r = 0.7; P = 0.003 using regression analysis). Adenomas and cancers showed further hypermethylation at this locus. Similarly, the MYOD gene showed age-related methylation in normal colon mucosa (r = 0.7; P < 0.00001 using regression analysis) and hypermethylation in cancers. Age-related methylation seems to be gene specific, because p16, THBS1, HIC-1, and CALCA were not affected. Furthermore, this process may also be modulated by tissue-specific factors. Our study suggests that aging is a major contributing factor to hypermethylation in cancer.
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PMID:Aging and DNA methylation in colorectal mucosa and cancer. 985 84

Carcinoma arising in pleomorphic adenoma of the salivary gland is a rare tumor, and its molecular aspects are unknown. Recent studies have revealed that malignant transformation of various human cancers may involve two different genetic alterations: inactivation of the p16 gene, which is a putative tumor suppressor gene, and genetic instability represented by microsatellite instability (MSI). However, so far, molecular investigations including p16 gene alteration and MSI have not been performed on carcinoma arising in pleomorphic adenoma. Both inactivation of the p16 gene and MSI were studied using DNA extracted from paraffin-embedded sections of carcinoma arising in pleomorphic adenoma. Samples also were analyzed for cyclin D1 gene amplification, which is thought to have oncogenic effects similar to those with inactivation of the p16 gene. One case showed the homozygous deletion of the p16 gene in the carcinoma, although hypermethylation of the p16 gene and amplification of the cyclin D1 gene were not observed in any cases. In two of four cases, MSI was observed. One case in two showed MSI in both the pleomorphic adenoma and the carcinoma. Results of this study suggest that two different genetic alterations, the inactivation of the p16 gene and genetic instability, play roles in the malignant transformation of carcinoma in pleomorphic adenoma. The MSI observed in the adenoma suggests that genetic alterations occur in pleomorphic adenoma.
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PMID:Deletion of the p16 gene and microsatellite instability in carcinoma arising in pleomorphic adenoma of the parotid gland. 991 33

Recent molecular studies have shown that there are differences in the prevalence and timing of certain molecular events between chronic ulcerative colitis (CUC)-associated dysplastic lesions and non-CUC-related sporadic adenomas. However, little is known regarding the molecular features of a specific subtype of CUC-related dysplasia-associated lesion or mass (DALM) that clinically, endoscopically, and pathologically resemble sporadic adenomas, and whether these lesions can be separated from non-CUC-related sporadic adenomas on the basis of their molecular genotype. Therefore, the purpose of this study was to evaluate loss of heterozygosity (LOH) of 3p, APC, and p16 in a specific group of CUC-associated "adenoma-like" DALMs and to compare the results of this tumor with those in a well-defined group of CUC-associated non-adenoma-like DALMs and non-CUC-associated sporadic adenomas. Polypectomy or resection specimens from 21 CUC patients with an adenoma-like DALM, 8 CUC patients with at least one nonadenoma-like DALM (12 lesions in total), and 23 non-CUC patients with a sporadic adenoma were evaluated for LOH of 3p, APC, and p16 by PCR analysis. The results were compared among the three different study groups and correlated with the clinical features of the patients and the pathology of their tumors. Chronic ulcerative colitis-associated adenoma-like DALMs showed LOH of 3p in five of 18 (28%) cases. This value was not significantly different from the 5% of non-CUC sporadic adenomas (p = 0.14) that were positive. However, 50% of CUC-associated non-adenoma-like DALMs were positive for LOH of 3p, and this value was significantly higher (p = 0.01) than the other groups. The frequency of LOH of APC did not differ significantly between the three patient groups (33%, 33%, and 43% in the three groups, respectively). Similar to the 3p results, CUC-associated adenoma-like DALMs and non-CUC-associated sporadic adenomas showed a similar low frequency of positivity for LOH of p16 (5% and 4%, respectively) in comparison to 56% of CUC-associated non-adenoma-like DALMs (p = 0.003). For all markers, no significant differences were detected in the CUC-associated adenoma-like DALM group between lesions that occurred within colitis compared with those that occurred in areas not involved by colitis. Chronic ulcerative colitis-associated non-adenoma-like DALMs have a different molecular genotype than CUC-related adenoma-like DALMs and non-CUC sporadic adenomas. Our data also suggests that the latter two groups of neoplasms may in fact represent a similar, if not identical, pathogenetic entity.
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PMID:Genetic alterations in chronic ulcerative colitis-associated adenoma-like DALMs are similar to non-colitic sporadic adenomas. 1097 94


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