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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In all normal cells, two type of genes, oncogenes and anti-oncogenes, are expressed and control cell proliferation and differentiation. Cell growth is stimulated by oncogenes and inhibited by anti-oncogenes. Cancerization involves loss of control due to defective gene expression either by overexpression of a normal protein (loss of quantitative control) or expression of an abnormal protein (loss of qualitative control). Several oncogenes have been identified. They include three oncogenes, c-myc, N-myc and L-myc, known to be overexpressed in small-cell carcinomas of the lung. Point mutations of the oncogene K-ras is found in 15 to 30% of adenoma carcinomas, especially in smokers. Loss of anti-oncogene function has also been described in processes leading to lung cancer. Chromosome abnormalities, for example the 3p14-23 deletion described in 1982, are found in 100% of small-cell carcinomas and in 50% of non-small-cell carcinomas. This deletion is never found in normal tissue. The gene involved has not yet been cloned. Other mutations or deletions include the RB gene, necessary for neuroendocrine differentiation, and the p53 gene which has undergone mutation in 50% of the non-small-cell carcinomas and 70% of the small-cell carcinomas. These acquired mutations are strongly associated with tobacco smoking. Oncogenes and anti-oncogenes play an important role in the complex step-wise process leading to cancerization. As tumour characterization becomes more precise and precancerous states better controlled, future treatments may relief on inhibiting tumoural growth by using drugs which would substitute for the lost effect of anti-oncogenes or inhibit activation of an oncogene. But at the present time, it is still difficult to define criteria predicting high risk of postoperative relapse or resistance and further studies investigating the correlation between genetic abnormalities and clinical staging and survival curves are required.
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PMID:[Oncogenes and anti-oncogenes in lung cancer]. 820 81

The expression of ras-P21 protein and gene alteration of the K-ras gene were examined in 12 cases of pleomorphic adenoma of the salivary gland. The tumor cells in all 12 cases were strongly stained for ras-P21 protein by the indirect immunoperoxidase method, suggesting the enhanced expression of ras-P21 protein in pleomorphic adenomas. Analysis of the PCR products for the K-ras gene by temperature-gradient gel electrophoresis (TGGE) revealed that gene alterations such as point mutations occurred in 4 out of 12 pleomorphic adenoma tissues examined.
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PMID:Expression of ras-P21 and ras gene alteration in pleomorphic adenomas. 824 43

Twenty-four sporadic colorectal adenomas were analysed for the presence of allelic loss on the short arm of chromosome 17 as well as mutations in the K-ras and p53 genes. Chromosome 17p13 allelic loss was not present in 14 out of 14 informative cases. K-ras mutations were observed in 15 out of 24 cases. A p53 gene mutation (GGC-->GAC at codon 245) was detected in two biopsies taken at a four year interval from a recurrent rectal villous adenoma. Both biopsies also contained the same K-ras gene mutation (GGT-->GTT at codon 12). The data from the recurrent rectal adenoma provide in vivo evidence that K-ras and p53 heterozygous mutations confer a proliferative advantage but together are not sufficient for malignant transformation.
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PMID:Genetic events in sporadic colorectal adenomas: K-ras and p53 heterozygous mutations are not sufficient for malignant progression. 831 95

To examine early genetic events during colorectal carcinogenesis, we searched for genetic alterations in 75 adenomas from seven patients with familial polyposis coli (FAP) and in 64 sporadic colorectal tumors (63 carcinomas and one adenoma). We investigated germ-line and somatic mutations in the APC gene, somatic mutations in the K-ras and p53 genes, and loss of heterozygosity (LOH) on chromosome 8p21-22. Thirty-two FAP adenomas carried detectable somatic mutations in the APC gene. The frequency of somatic APC mutations among adenomas was the same regardless of differences in size or histopathological classification. On the other hand, K-ras mutation was very rare in small adenomas where dysplasia was mild or moderate but frequent in large adenomas with severe dysplasia. Mutation of the p53 gene was observed in only two adenomas and LOH on 8p22 was detected in none. These results imply that a second 'hit' in the APC gene, but not necessarily mutation in K-ras or p53, is an important and critical event for formation of a colorectal adenoma.
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PMID:Detailed analysis of genetic alterations in colorectal tumors from patients with and without familial adenomatous polyposis (FAP). 839 78

Ras mutations are an important early event in a number of carcinogen-induced rodent tumors. Colon carcinogenesis induced in rats by azoxymethane is a useful model as it mimics the adenoma-carcinoma sequence observed in humans. In addition, aberrant crypt foci develop in the rat and these lesions appear to be potentially important precursors to adenomas in colorectal cancer. Recent studies have shown that specific K-ras codon 12 and 13 mutations are present in up to 66% of carcinogen-induced rat colon adenocarcinomas. We studied the frequency of these mutations during the aberrant crypt focus-adenoma-carcinoma sequence in azoxymethane-induced Fisher F344 rats. K-ras codon 12 GAT and codon 13 GAC mutations were detected with a sensitive assay based on the amplification of DNA using the polymerase chain reaction. No mutations were present in normal mucosa. Of 27 aberrant crypt foci, K-ras mutations were identified in 2 lesions containing 5 and 10 aberrant crypts, respectively. Mutations were present in 1 of 23 and 10 of 27 adenomas and adenocarcinomas, respectively. These data suggest that K-ras mutations play a role during the stages of carcinogenesis in azoxymethane-induced rat colon cancer. The demonstration of a genetic mutation in aberrant crypt foci provides further evidence for the significance of these lesions as precursor markers of malignant potential during colorectal tumorigenesis.
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PMID:K-ras mutations in aberrant crypt foci, adenomas and adenocarcinomas during azoxymethane-induced colon carcinogenesis. 840 99

Gene changes in multiple oncogenes, multiple growth factors and multiple tumor-suppressor genes are observed in stomach cancer. Among them, those most commonly implicated in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma are inactivation (mutations and allele loss) of the p53 gene, and activation (abnormal expression and amplification) of the c-met gene. Moreover, they occur at an early stage of stomach carcinogenesis. In addition, loss of heterozygosity (LOH) on chromosome 5q (APC locus) is frequently associated with well-differentiated adenocarcinoma. LOH on chromosome 18q (DCC locus) and LOH of the bcl-2 gene also are common events of well-differentiated adenocarcinoma. LOH on chromosomes 1q and 7q may be involved in the progression of well-differentiated adenocarcinoma. Conversely, the development of poorly differentiated adenocarcinoma, in addition to changes in p53 and c-met genes, requires reduction or dysfunction of cadherin. Overexpression of bcl-2 protein is observed in poorly differentiated adenocarcinoma or signet-ring cell carcinoma. Moreover, the K-sam gene is amplified preferentially in poorly differentiated adenocarcinoma of scirrhous carcinoma. K-sam amplification in scirrhous carcinoma often occurs independently of c-met gene amplification. LOH on chromosome 1p also is relatively common in poorly differentiated adenocarcinoma. Exceptionally, signet-ring cell carcinoma shares APC mutations. There are some differences in expression of the growth-factor/receptor system between well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma. Moreover, interaction between cell-adhesion molecules in tumor cells expressing c-met and hepatocyte growth factor (HGF) from stromal cells is linked with morphogenesis of two histological types of stomach cancer. Intestinal metaplasia and adenoma of the stomach also contain p53 mutations and K-ras mutations or tpr-met rearrangement. Taken together, different genetic pathways of stomach carcinogenesis may exist for poorly differentiated and well-differentiated stomach cancers. Some of the latter may develop by a cumulative series of gene alterations similar to those of colorectal cancer.
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PMID:Molecular mechanism of stomach carcinogenesis. 844 Jul 43

The frequency of activating mutations at codons 12 and 13 of the K-ras gene was investigated in 57 sporadic adenomas from 47 patients using the polymerase chain reaction and oligonucleotide hybridisation assay. Sixty eight per cent of the adenomas tested were positive for K-ras mutations. This high frequency, combined with the lack of a correlation between mutations and adenoma size, suggest that K-ras mutations occur earlier in the adenoma-carcinoma sequence than has previously been suggested. The high frequency observed in sporadic adenomas contrasts with the reported low frequency (18%) in adenomas from patients with familial adenomatous polyposis (FAP), suggesting a possible difference in the molecular genesis of FAP and non-FAP adenomas. Finally, it was found that adenomas from patients with a personal history of colorectal cancer were more likely to contain a K-ras mutation than those from patients with no such history. This is a new finding and worthy of further study.
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PMID:High frequency of K-ras mutations in sporadic colorectal adenomas. 847 89

The frequency of p53 overexpression and K-ras codon 12 mutation was investigated in a series of colorectal adenomas. p53 was detected by immunohistochemistry in only 5% of tumours, whereas K-ras mutation was found in eight of 30 adenomas examined. In vitro, mutant p53 and ras genes cooperate to transform primary rat cells into a tumourigenic cell line. The presence of both p53 overexpression and K-ras mutation in a benign tubulovillous polyp in the present series suggests that in vivo this combination of events is insufficient to cause malignant transformation of a large bowel adenoma.
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PMID:p53 expression and K-ras mutation in colorectal adenomas. 850 62

To elucidate genetic alteration in relation to morphology and also to confirm more directly the proposed adenoma-carcinoma sequence, we analyzed thirty-eight colorectal "cancer in adenoma" lesions exhibiting areas of different atypia, in terms of K-ras codon 12 point mutation. The mutation incidence was 26.3% (10/38) for all cancerous areas. Well-differentiated and very well-differentiated carcinoma exhibited values of 17.6% (3/17) and 30.4% (7/23), respectively (statistically not significant). Positive cases of adenoma with severe atypia and adenoma with moderate or slight atypia were 26.7% (8/30) and 8.3% (3/36) respectively (statistically significant). Thus, K-ras point mutation, as indicated previously, may play an important role in the early stages of colorectal tumorigenesis. As for the nature of the mutation, GGT(Gly) to GAT(Asp) was the most frequent (80%). Eight cases had mutations concurrently in different areas of the same tumor and in all of these the mutation was homogeneous (6 cases to GAT, 1 case to TGT and 1 case to GTT). This provides genetic support for the "adenoma-carcinoma sequence" theory proposed on the basis of morphological considerations. All lesions with a mutation were of polypoid type, and no mutation was found in the flat type.
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PMID:Variation in K-ras codon 12 point mutation rate with histological atypia within individual colorectal tumors. 851 5

The relationship between the development of peripheral lung lesions induced by tobacco-specific 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and K-ras gene mutation in A/J mice, and the correlations between histological alterations and the course of lung lesion development after NNK treatment and K-ras gene mutation were investigated. The acquisition of a selective growth advantage by the lung lesions with mutations was also examined using immunohistochemical labeling with bromodeoxyuridine. Thirty female 5 weeks old A/J mice were each injected intraperitoneally with a single dose of NNK (100 mg/kg body weight) and subdivided into 6 groups according to the time after NNK treatment. The lung lesions were characterized histologically as alveolar/bronchiolar hyperplasia, adenoma and adenocarcinoma, and point mutations in codons 12 and 61 of the K-ras gene were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and dideoxy sequencing methods. K-ras gene mutations were identified in 7 (58.3%) of 12 hyperplasias, 42(75.0%) of 56 adenomas and 3 (75.0%) of 4 adenocarcinomas. The most frequent K-ras gene mutation was a G-to-A transition at the second base of codon 12 and this accounted for 86.5% of all the mutations detected. Neither the frequency of activation of this gene nor the specific mutation was affected by the time after NNK treatment and there was no positive correlation between the proliferative activity of lung lesions and the presence of K-ras gene mutations. Thus, K-ras gene mutation is closely associated with the development of NNK-induced peripheral lung lesions in A/J mice, but it plays no role in the selective growth advantage of these lesions.
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PMID:Effects of K-ras gene mutations in the development of lung lesions induced by 4-(N-methyl-n-nitrosamino)-1-(3-pyridyl)-1-butanone in A/J mice. 860 47


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