Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a total of 26 primary human lung tumors and 60 metastases derived from them, exons 5-8 of the p53 tumor suppressor gene were analyzed by single-strand conformation polymorphism and subsequent direct DNA sequencing of amplified DNA. Mutational inactivation of the p53 gene was identified in four of five squamous cell carcinomas, three of nine adenocarcinomas, and two of nine small-cell carcinomas, the overall incidence being 35%. Point mutations occurred at a similar incidence in exons 5-8, with a preference for G-->T transversions. In seven of nine cases (78%), mutations were identical in the primary tumor and all of its metastases, indicating that in lung tumors, p53 mutations usually precede metastasis and that hematogenic and lymphogenic dissemination of tumor cells to other tissues is not associated with a selection against p53 inactivation. In one case, a kidney metastasis had the same mutation as the primary squamous cell carcinoma, whereas a liver metastasis had no mutation, indicating heterogeneity of the primary lung neoplasm and selective metastasis of mutated and nonmutated tumor cells to kidney and liver, respectively. Only in one liver metastasis was a mutation identified that was neither present in the primary lung tumor nor in a kidney metastasis, suggesting that occasionally p53 mutations occur after metastatic spread.
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PMID:p53 mutations in primary human lung tumors and their metastases. 814 8

Simultaneous multiple gastric cancers are rarely observed in clinical practice, and its association with p53 gene mutation has not been mentioned in any previous reports. We report a case of advanced gastric cancer with two primary lesions in the stomach who received total gastrectomy. Tumor and surrounding normal tissues from the surgical specimen were studied by using polymerase chain reaction-single strand conformation polymorphism analysis, restriction enzyme digestion method and direct sequencing. Point mutations of p53 gene at codon 248 (CGG-->TGG) were found in both primary tumor foci. The patient developed cancerous peritonitis eight months after the operation and expired six months later. This report suggests that p53 gene mutation can occur at an earlier stage in the tumorigenesis of gastric cancer than previously reported and it might be associated with an unusual clinical and pathological presentation.
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PMID:A case of simultaneous multiple gastric cancers with p53 gene mutation. 817 66

The selection of patients with axillary lymph node-negative breast cancer who should receive adjuvant therapy today is confused by an expanding arsenal of putative prognostic factors. The size of the primary tumor remains the dominant factor in sorting among this group of patients, with general agreement that tumors 1 cm or less should be spared adjuvant systemic therapy outside of a clinical trial. There are a few favorable histologic subgroups that may be added to this excluded group: ductal carcinoma in situ and pure tubular, papillary, and typical medullary tumors. For the larger tumor (generally > 2 cm in diameter, but always > 3 cm), there is little disagreement that adjuvant therapy is indicated. The host of additional prognostic factors are directed mainly toward the group of tumors that fall between these two categories. Nuclear grade, S-phase, and perhaps p53 mutations influence decisions for treatment by their elevation. Although the decision remains with the patient and the recommendation with the mature judgment of the clinician, the prognostic indicators available continue to multiply. That an indicator can retrospectively sort prognosis is of limited interest. It requires prospective validation in another patient population, reproducibility in other laboratories, and multivariate analysis among factors measured on the same population of patients to integrate a factor into clinical decision-making. It is only beginning to be accomplished. The next generation of factors being sought are those that predict for response or lack of response to specific therapies, rather than merely indicating natural history. Estrogen and progesterone receptors are the prototypes of this class of indicators.
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PMID:Integration of risk factors to allow patient selection for adjuvant systemic therapy in lymph node-negative breast cancer patients. 819 75

Mutations affecting the p53 gene are associated with many human malignancies, but little is known about changes in p53 in unknown primary tumors (UPTs), which are characterized as tumors with advanced stages of malignancy. We therefore investigated the frequency of p53 mutations in a series of 15 unknown primary tumor biopsies and eight cell lines established from UPTs. Mutations in the conserved regions of the p53 gene were verified by single-strand conformation polymorphism analysis of exons 5-9 and were verified by direct DNA sequencing of polymerase chain reaction products. A point mutation leading to an amino acid change in the p53 protein was found in six cases, and a mutation causing a change to termination was found in one case. A frameshift mutation was observed in one cell line. In one patient and one cell line we observed more than one mutation in the p53 coding sequence. Overall, the frequency of mutations that changed the p53 coding sequence in the UPTs we studied was 26% (6/23). Mutations were distributed in eight codons of the p53 gene. Seven of these tumors showed a reduction to homozygosity at the p53 allele, but one tumor apparently retained heterozygosity. We conclude that although UPTs represent highly metastatic advanced tumors that are expected to have a high incidence of p53 mutations, the frequency of p53 mutations is relatively low, suggesting that p53 mutations may not play a major role in the development and progression of this unique tumor type.
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PMID:p53 gene mutation spectrum in human unknown primary tumors. 823 43

Mutations in, and aberrant expression of, the p53 tumor suppressor gene were assessed in 17 cell lines derived from human malignant brain tumors (glioblastoma multiforme). Exons 5 through 8 were screened by single strand conformational polymorphism analysis (SSCP), followed by direct DNA sequencing. Mutations were found in 6 of 17 glioma cell lines, i.e., at a frequency similar to that found in primary malignant gliomas. Loss of the wild type allele was observed in 4 of the mutated cell lines. Two cell lines had the same mutation (CGG-->TGG; Arg-->Trp) in codon 248. Five of 6 mutations were transitions, 4 of which occurred at CpG dinucleotides. In one cell line a 10-bp deletion at the intron 4/exon 5 junction was found. Five of 6 glioma cell lines contained a mutation identical to that in the respective primary tumor despite prolonged in vitro culture (140-221 passages). Thus, the acquisition of p53 mutations during culture appears to be infrequent. Two cell lines derived from heterozygous tumors maintained the wild type p53 allele during long term culture. p53 protein levels were assessed by immunofluorescence cytochemistry and immunoprecipitation followed by Western blot analysis and revealed elevated levels of the p53 protein, although to a variable extent, in all cell lines with p53 mutations. A marked p53 protein accumulation was also observed in two cell lines lacking p53 mutations in exons 5 through 8, indicating that a prolonged half life of the gene product is not solely dependent on an aberrant coding sequence. The remaining cell lines had either low levels or no detectable p53 protein; one of the latter contained a gross rearrangement of the p53 gene. Our results suggest that with respect to p53 gene status, glioma cell lines usually resemble the original tumors and may, therefore, be suitable for studying the biological changes associated with p53 mutations in glial tumors.
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PMID:p53 protein accumulation and gene mutations in human glioma cell lines. 825 36

Diffuse large cell lymphomas are aggressive tumors of B-cell origin. In some cases they arise from low-grade follicular lymphomas carrying the t(14;18) translocation, an event that leads to the overexpression of the BCL-2 gene product. More frequently, however, they lack the t(14;18) translocation. Rearrangements of the c-MYC proto-oncogene and mutations of the p53 tumor suppressor gene have also been documented in these lymphomas. This study examines the extent to which alterations in the BCL-2, c-MYC, and p53 genes co-exist within individual lymphomas. Eight diffuse large cell lymphoma cell lines and 11 diffuse large cell lymphoma tumors were assessed for genetic alterations in these three genes. Our results indicate that there is a heterogeneity in the oncogene/suppressor gene profile among diffuse large cell lymphomas. Two cell lines and one tumor carried alterations in all three genes, one cell line carried alterations of c-MYC and p53, and one primary tumor and one cell line carried p53 mutations and the t(14;18). Single alterations of BCL-2 and p53 were also observed. Another cell line had no alterations in any of these genes. The heterogeneity indicates that varied mechanisms may be involved in the generation of diffuse large cell lymphomas.
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PMID:Alterations of the p53 tumor suppressor gene in diffuse large cell lymphomas with translocations of the c-MYC and BCL-2 proto-oncogenes. 827 34

We have studied the frequency of mutations in the p53 gene in human prostate cancer. The investigated material consisted of 20 primary-tumor tissue specimens, obtained by transurethral resection and tissue specimens of 15 lymph-node metastases, obtained at total prostatectomy. The applied methods encompassed immunohistochemistry on frozen sections, using the monoclonal antibody PAb 1801, and single-strand conformation polymorphism (SSCP) analysis, after amplification of single exon sequences by PCR, on exons 5 to 8 of the p53 gene. The mutations, leading to aberrantly migrating bands in the PCR-SSCP analysis, were identified by direct sequencing of the PCR product. Immunohistochemical and PCR-SSCP analysis were completely confirmative. In the primary tumors, mutations were found in 10% of the specimens (codons 232 and 273), and in lymph-node metastases in 15% of the specimens (codons 248 and 273). In one case (codon 273), the same mutation was found both in the primary tumor and in the lymph-node metastasis. Our results show that p53 mutations are infrequent in both primary and metastatic prostate tumors. In addition, they indicate that there is no strict correlation between p53 mutation and tumor metastasis.
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PMID:Frequency and characterization of p53 mutations in primary and metastatic human prostate cancer. 831 37

The ELM erythroleukemia is novel in that long-term survival of leukemic cells in culture (ELM-D cells) is dependent on contact with a bone marrow-derived stromal feeder cell layer. However, a number of stroma-independent (ELM-I) mutants that vary in their ability to differentiate in vitro in response to erythropoietin and interleukin-3 have been derived. We have attempted to define the genetic changes responsible for these different phenotypes. At the p53 locus in the primary leukemic cells, one copy of the gene has been lost whereas the other contains an 18-bp depletion, implicating its mutation as an early step in the development of the leukemia. Changes in ets gene expression have also been found. The Fli-1 gene region is rearranged in the primary tumor because of the insertion of a retrovirus inserted upstream of one Fli-1 allele, but this does not result in Fli-1 gene activation in any of the ELM-D or ELM-I cell lines except one. It seems significant that this line is the only one to have lost the ability to differentiate in response to erythropoietin. In addition, up-regulation of erg is associated with stromal cell-independent growth, since all ELM-I mutants have moderate levels of erg mRNA, whereas only low or undetectable levels are found in primary leukemic cells in vivo or in ELM-D cells in vitro. This up-regulation of erg mRNA seems to be important for stromal cell-independent growth, since ELM-D cells show elevated expression of the erg gene after separation from stromal cells. This seems to be made permanent in ELM-I mutants, since they do not down-regulate erg mRNA when grown in contact with stromal cells. We therefore propose that ets family members regulate both the survival and differentiation of erythroid cells.
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PMID:Differentiation arrest and stromal cell-independent growth of murine erythroleukemia cells are associated with elevated expression of ets-related genes but not with mutation of p53. 835 1

The spectrum of p53 gene mutations was determined in formalin-fixed, paraffin-embedded samples of small-cell lung cancer derived from 28 patients. By direct sequencing of exons 5, 7, and 8, including their flanking intron sequences, 18 mutations were identified in 17 tumors (61%), and in all but two of these the wild type allele was lost. In 8 cases, the mutation detected in the tumor was absent from the corresponding normal tissue, indicating that these mutations were somatically acquired. In two patients, identical mutations were found in the primary tumor and corresponding metastases. In a further case, an intrapulmonary metastasis did not show the mutation detected in the primary tumor. The local distribution of the mutations resembled that reported in non-small cell lung cancer and gave no indication of distinct bot spot regions. G-to-T transversions were the predominant type of mutation, reflecting a possible genotoxic influence of carcinogens contained in tobacco smoke. Mutations were equally distributed among tumors with intermediate and oat cell histology and did not show a significant association to age and gender of the patients. Also, no significant relationship was observed between the presence of a mutation and tumor stage (T, N, M) or survival. However, transitions at CpG dinucleotides were restricted to tumors without detectable metastases at the time of biopsy, whereas all other mutations occurred in metastasizing small cell lung cancer.
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PMID:Mutational spectrum of the p53 gene in human small-cell lung cancer and relationship to clinicopathological data. 838 8

The effect of the human papillomavirus (HPV) oncogenes E6 and E7 was examined in transgenic mice with a construct containing the human beta-actin promoter regulating HPV16 E6 and E7 open reading frames. In the sole line of mice that transmitted the transgene, neuroepithelial tumors appeared at 2.5 months of life, and by 10 months, 87 of 122 (71%) of the animals were dead from brain tumors. The most frequent type of tumor (74%) was an anaplastic neuroepithelial tumor associated with the ependyma of the third and fourth ventricles, which locally invaded adjacent brain tissue and spread for considerable distances along the ventricular surface. The other two types of tumor were well-differentiated choroid plexus carcinomas (26%) and rare pituitary carcinomas (8.7%). HPV16 E6 RNA and E7 oncoprotein expression were demonstrated in tumor tissue and primary cell lines derived from the tumors. Examination of two tumor suppressor gene products, the retinoblastoma protein and p53, known to bind to HPV16 E7 and E6 oncoproteins, respectively, showed both were expressed in the primary tumor cell lines. These data support a causative role for the HPV oncoproteins in epithelial carcinogenesis.
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PMID:Neuroepithelial carcinomas in mice transgenic with human papillomavirus type 16 E6/E7 ORFs. 838 43


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