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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have demonstrated that genes of the ras family (H, K, and N) can be activated by point mutations at codons 12, 13, and 61. In the present study we have used oligonucleotide probes corresponding to these regions to assess the role of ras gene mutations in the genesis of human rhabdomyosarcoma. To increase the sensitivity of this method the appropriate regions of the three ras genes were first amplified using the polymerase chain reaction. The results show that 35% (5/14) embryonal rhabdomyosarcomas investigated contain mutations in the N-ras or K-ras genes. Thus ras gene mutation is implicated in the development of mesenchymal and embryonal tumors in addition to its previously documented role in epithelial and hematological neoplasia.
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PMID:Detection of point mutations in N-ras and K-ras genes of human embryonal rhabdomyosarcomas using oligonucleotide probes and the polymerase chain reaction. 268 62

The frequency of ras (H-, K-, and N-ras) and c-myc oncogenes was investigated in multiple myeloma (MM). By means of the polymerase chain reaction (PCR)/oligonucleotide hybridization method, DNA from 56 tumor biopsies was analyzed for the presence of activating mutations involving codons 12 and 61 of the H-, K-, and N-ras genes and codon 13 of the N-ras gene. Mutations, involving the N- or K-ras genes, were detected in 18 of 56 (32%) cases of which 12/43 (27%) were at diagnosis and 6/13 (46%) were after treatment. In some cases, multiple mutations affecting different ras alleles were detected. Direct nucleotide sequence analysis of PCR products indicated that a more heterogeneous nature of the base pair changes than previously shown for other tumors along with a preferential involvement of N-ras codon 61. The heterogeneity of MM cases with respect to the presence of ras oncogenes prompted an analysis of possible correlations with different clinico-pathologic characteristics of MM from which a correlation between the presence of ras oncogenes and a partial or complete lack of response to therapy emerged. The frequency of activating rearrangements or mutations of the c-myc gene were studied by Southern blot analysis and PCR sequencing, respectively. However, contrary to previous reports involving mostly MM cell lines, no structural alterations of the c-myc gene were found. These results indicate that ras, but not c-myc, oncogenes are activated in vivo in MM cells, representing the first oncogene alteration that has been associated at appreciable frequency with this type of malignancy. While the mechanism of occurrence and biological role of ras activation in MM remains to be elucidated, the preliminary correlations observed in this study between the presence of ras oncogenes and poor therapeutic response suggest that further investigations of the possible prognostic significance of these alterations are necessary.
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PMID:Ras oncogene mutation in multiple myeloma. 268 17

Efforts to investigate the progression of events that lead human cells of epithelial origin to become neoplastic in response to carcinogenic agents have been aided by the development of tissue culture systems for propagation of epithelial cells. We have recently developed an in vitro multistep model suitable for the study of human epithelial cell carcinogenesis. Primary human epidermal keratinocytes acquired indefinite lifespan in culture but did not undergo malignant conversion in response to infection with Adl2-SV40 virus. Subsequent addition of Ki-MSV, which contains a K-ras oncogene, to these cells induced morphological alterations and the acquisition of neoplastic properties. Nontumorigenic human epidermal keratinocytes immortalized by Adl2-SV40 virus (RHEK-1) were also transformed by treatment with chemical carcinogens (MNNG or 4NQO) and by X-ray irradiation. Such transformants showed morphological alterations and induced carcinomas when transplanted into nude mice. This in vitro system may be useful in assessing environmental carcinogens for human epithelial cells and in detecting new human oncogenes since ras oncogenes were not activated in these chemical--or X-ray--transformed RHEK-1 lines. Subsequently, it was found that this line could be transformed neoplastically by a variety of retroviruses containing H-ras, bas, fes, fms, erbB and src oncogenes. In addition, our recent results indicate that nontumorigenic RHEK-1 cells can be transformed following transfection with an activated human oncogene. Thus, this in vitro system may be useful in studying the interaction of a variety of carcinogenic agents and human epithelial cells. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of tumor viruses and chemical carcinogens or X-ray irradiation and support a multistep process for neoplastic conversion. Further, evidence for the multistep nature of neoplastic transformation of human epithelial cells in vitro using other model systems is presented.
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PMID:Neoplastic transformation of human epithelial cells in vitro. 268 34

Adult Atlantic tomcod collected from the Hudson River slightly north of New York City have an extremely high incidence (55-90%) of histologically defined hepatocellular carcinomas, whereas tomcod from control sites in Maine or Rhode Island exhibit little evidence of this condition. Genomic DNA was isolated from Hudson tomcod tumors and from normal Hudson and Saco River, Maine tomcod livers and tested for transforming activity in the NIH3T3 transfection assay. Six out of nine tumors (66%) tested proved positive. Southern blot analysis of all primary (6/6) transfectant and nude mouse tumor DNAs revealed evidence of an exogenous tomcod K-ras gene, while no activation of the H-ras gene was observed. These studies demonstrate that an outbred population of fishes and inbred mammals suffer genetic alternations at the same oncogene loci and suggest that similar pathways to neoplasia may be operative in both systems. Oncogene activation in naturally exposed feral populations may prove a particularly sensitive marker of environmental degradation in aquatic systems.
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PMID:Activation of the K-ras oncogene in liver tumors of Hudson River tomcod. 268 54

We have used polymerase chain reaction (PCR), an amplification procedure, and oligonucleotide hybridization to detect ras gene point mutations in DNA from melanoma tumor samples. Genomic DNA was examined from 40 specimens of melanotic lesions, including benign nevi, primary melanomas, lymph node metastases, and systemic metastases. Adjacent normal skin or peripheral blood was analyzed as control material in 28 cases. ras mutations were detected overall in 25% of malignant tumors. In addition, mutations of all three ras genes were detected. We observed ras mutations in 2 of 4 benign atypical nevi (2 X K12), 4 of 22 primary melanomas (3 X K12, 1 X H12, 1 X N61), and 4 of 14 secondary (5 X K12, 1 X N61) tumors. One with a primary melanoma had concurrent K12 and H12, and two patients with secondary tumors had concurrent K12/N61 and K12 Asp/K12 Val mutations, respectively, making a total of 10 of 40 (25%) patients with ras mutations. This is the first demonstration of K-ras mutations in human melanoma. The presence of K-ras mutations in nevi, putative melanoma precursors, suggests that ras activation may be an early event in melanoma development. No correlation between tumor thickness and the presence of a ras mutation was observed.
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PMID:ras mutations in human melanotic lesions: K-ras activation is a frequent and early event in melanoma development. 269 57

A new cell line (KT21-MG1) has been established from a human malignant meningioma transplanted into nude mice. The cultured cells showed epithelial cell-like morphology and were positive immunohistochemically for vimentin as the original tumor. They have been grown continuously in vitro for more than 2 years. The population doubling time was about 24 hours at the 30th passage. The cells are capable of proliferating in soft agar medium and produced tumors in nude mice, the histologies of which were similar to the original patient-derived tumor. Analysis of cellular oncogenes showed that myc and fps were amplified approximately tenfold and threefold, respectively, in this cell line, whereas N-myc, L-myc, N-ras, K-ras, H-ras, abl, erbB2, Blym, src, raf-1, myb, and sis were not changed significantly. The amplification of myc was accompanied by an enhanced expression. Chromosome studies of cultured cells showed the monosomy of chromosome 22 that has been reported to be a specific abnormality in meningiomas.
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PMID:Establishment of a human malignant meningioma cell line with amplified c-myc oncogene. 280 14

Skin fibroblasts derived from three patients with familial polyposis coli (FPC) were treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) alone or in combination with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). None of the cultures treated four times with MNNG alone (1 microgram/ml) or in combination with TPA (eight applications, 0.1 microgram/ml each) showed either morphological transformation or anchorage-independent growth for 18 months after treatments. FPC cells treated with MNNG alone showed cell growth inhibition, breakage and loss of chromosomes, as well as the deletion of 5.7 kilobase (kb) EcoRI fragment in the c-K-ras locus as detected by Southern blot analysis with v-K-ras specific probe (clone KBE-2). The control cells contained two EcoRI fragments of 5.7 and 4.2 kb. On the other hand, cells treated with MNNG first and then followed by treatment with TPA not only showed an increase in the rate of cell growth but also exhibited two novel EcoRI fragments of 9.4 and 12 kb. Treatment with TPA alone appeared to stimulate cell division long after application and to induce chromosomal aberrations but had no effect on c-K-ras sequences. The most likely explanation for the appearance of chromosome pulverization and hyperploidy in FPC cells treated with TPA is the induction of premature chromosome condensation of the S phase cells due to fusion with the mitotic chromosomes.
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PMID:Chromosomal and c-K-ras oncogene alterations induced by a chemical carcinogen and phorbol ester in skin fibroblasts of individuals with familial polyposis coli. 284 31

It is difficult to identify early ovarian cancer at present. However, some tumor markers (CA125, CA19-9, CEA) and soon imaging system (MRI, CT, UT) and some oncogenes are available for diagnosis of ovarian cancer recently. Multivariate analysis of tumor markers has a possibility of stage I cancer. MRI is very useful to identify some cystic and hemorrhagic lesions. Amplifiers of N-myc and K-ras may be applied to diagnose ovarian cancer. In future, these new technologies may identify early ovarian cancer.
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PMID:[New technology of diagnosis of ovarian cancer]. 284 69

We have examined alterations in six oncogenes--H-ras, K-ras, N-ras, myc, fos, and N-myc--in nine primary human colon tumors. Tumors were obtained within an hour of resection; as a control for each tumor, adjacent normal colon tissue was also obtained. Deoxyribonucleic acid extracted from each tissue sample was assayed by digesting with appropriate restriction endonucleases and, after gel electrophoresis and transfer to nitrocellulose, hybridizing with radiolabeled oncogene probes. Amplification of the myc locus, relative to adjacent normal colon tissue, was observed in two of these tumors; by dot-blotting, it was estimated that myc was amplified twofold to fivefold in each tumor. No rearrangements of myc, however, were observed in any of these tumors. Examination of the H-ras alleles of these nine tumors revealed that eight possess only "common" alleles of this gene, and that each was identical to its control. Normal colon DNA of the ninth patient, however, was found to possess both a "common" and a "rare" allele, and the "common" allele of H-ras appeared to be deleted in the tumor DNA of this patient. A restriction polymorphism indicative of a mutation in the 12th codon of K-ras was not found in any of these tumors, and we observed no evidence of rearrangement of amplification of the N-ras, K-ras, fos, or N-myc genes.
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PMID:Oncogene alterations in primary human colon tumors. 287 25

To define the role of cellular oncogenes in human cancers, we studied the prevalence of mutational activation of ras oncogenes in untreated non-small-cell lung cancer. Genomic DNA was extracted from 39 tumor specimens obtained by thoracotomy and was examined for activating point mutations in codons 12, 13, and 61 of the H-ras, K-ras, and N-ras genes. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. The K-ras gene was found to be activated by point mutations in codon 12 in 5 of 10 adenocarcinomas. Two of these tumors were less than 2 cm in size and had not metastasized. No ras gene mutations were observed in 15 squamous-cell carcinomas, 10 large-cell carcinomas, 1 carcinoid, 2 metastatic adenocarcinomas from primary tumors outside the lung, and 1 small-cell carcinoma. An approximately 20-fold amplification of the unmutated K-ras gene was observed in a tumor that proved to be a solitary lung metastasis of a rectal carcinoma. We conclude that mutational K-ras activation may be an important early event in the pathogenesis of adenocarcinoma of the lung but that amplification of ras genes or mutational activation of H-ras or N-ras does not play a major part in non-small-cell lung cancer.
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PMID:Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung. 304 Dec 18


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