Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nasopharyngeal carcinoma (NPC) is the third most common cancer in the southern provinces of China, but a rare cancer in other parts of the world. Epidemiological studies suggested a multifactorial etiology of NPC involving infection of Epstein Barr virus (EBV), genetic predisposition, environmental factors, such as consumption of salted fish, and other unknown factors. p53 mutation is a common event in many forms of human cancers but its possible involvement in the pathogenesis of NPC has not been examined. The presence of p53 mutation in NPC is studied by the sensitive PCR-SSCP analysis and direct DNA sequencing method. The frequent sites of p53 mutation (exons 4 to 8) reported in other human tumors were studied. Thirty-eight biopsied tumors of NPC and 4 NPC cell lines were examined for the presence of p53 mutation. No mutation of p53 resulting in change in amino acid sequence of the encoded p53 protein was identified in any of the biopsies tumors. RFLP studies of the biopsied materials of NPC also revealed no loss of heterozygosity at chromosome region 17p13 in 15 out of 15 informative cases, which further supports the conclusion that p53 mutation is an infrequent event in NPC. Apparently, p53 mutation has no significant role in the pathogenesis of this special group of human cancers. However, p53 mutation is frequently observed in cell lines derived from the primary NPC tumors. All the three NPC cell lines examined carry a missense p53 mutation, suggesting that mutation of the p53 gene may confer growth advantage to the tumor cells to become established in culture.
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PMID:p53 mutation in human nasopharyngeal carcinomas. 129 43

Using the polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis, we have examined the highly conserved regions of the p53 gene in 58 biopsy samples of head and neck tumors. Mutations were found in 13/58 (23%) tumor specimens, but not in 6 normal tissues. Ten of 13 mutations were due to single base changes and the remaining 3 were 1- or 8-base deletion mutants. These mutations were clustered in exons 5 and 7 and resulted in amino acid changes. Our results seem to indicate that mutations in the p53 gene contribute to a significant number of cases of the head and neck tumors including 20% of nasopharyngeal carcinoma biopsies. The relationship of Epstein-Barr virus or human papillomavirus and p53 gene mutations in this group of cancers was also analyzed and discussed.
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PMID:Detection of mutations in the p53 gene in human head and neck carcinomas by single strand conformation polymorphism analysis. 133 31

p53 tumour suppressor gene is often found mutated in Burkitt's lymphoma (BL) cell lines and tumours. We analysed 35 BL tumours for the accumulation of p53 protein, and correlated the results with DNA flow cytometric data on the proliferative activity (SPF), and data on the presence or absence of Epstein-Barr virus (EBV) DNA. More than one-third (37 per cent) of the tumours showed accumulation of p53, which was considered to be consistent with mutation of the p53 gene. Tumours that were positive both for EBV DNA and p53 had significantly higher mean SPF than corresponding EBV DNA negative and/or p53 negative tumours. The proportions of tumour cells with accumulation of p53 appeared to correlate with tumour SPF only in EBV DNA positive BLs. However, there was no apparent association between accumulation of p53 and the presence or absence of EBV DNA. These findings are suggestive of multiple pathways in BL tumour progression.
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PMID:Accumulation of p53 protein correlates with tumour proliferative activity in EBV positive Burkitt's lymphoma. 133 33

Nasopharyngeal carcinoma (NPC) is a malignancy which is consistently associated with the Epstein-Barr virus (EBV). The structure of the EBV genome in NPC suggests that NPC is a clonal proliferation of epithelial cells which emerges after EBV infection. The disease develops with high incidence in specific populations in discrete geographic locations, implicating possible genetic or environmental cofactors. Mutations of the p53 gene are among the most frequent genetic changes found in a large variety of human tumors. Mutations in p53 have been shown to abrogate the suppressor function of wild-type p53 and thus contribute to the transformed phenotype. To determine if mutation in p53 participates in the development of the malignant clone in NPC, the structure and sequence of p53 in 42 primary, metastatic, and nude mouse-passaged NPC specimens was analyzed. A high frequency (6 of 9) of mutations was detected in the nude mouse-passaged tumors, while only 2 of 15 metastatic and 0 of the 18 primary tumors harbored mutant p53. The p53 mutations included single-point mutations and more extensive changes such as frame shifts, deletion, duplication, or complete loss of coding sequences. These data indicate that alterations of the p53 gene are unlikely to be involved in the initial genetic events leading to the clonal outgrowth in NPC. However, although it is a rare NPC which can be established in nude mice, this growth advantage appears to be conferred on tumors bearing a mutant p53.
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PMID:Alterations of the p53 gene in nasopharyngeal carcinoma. 134 27

Lymphoid neoplasms, like all malignant tumors, arise as a consequence of the accumulation, in a single cell, of a set of genetic lesions that result in altered proliferation or increased clonal life span. The most frequently observed genetic abnormalities among the malignant non-Hodgkin's lymphomas are translocations, which appear to be lineage and, to a large extent, lymphoma specific. Recombinases that normally mediate the process of antigen receptor gene rearrangement appear to have an important (but not exclusive) role in the mediation of these translocations and of other types of gene fusion (e.g., deletion of intervening DNA). Frequently, such fusions result in the increased or inappropriate expression of crucially important proteins, many of which are transcription factors that regulate the expression of other genes. These abnormalities, however, do not appear to be sufficient to induce lymphoma, and it is likely that the additional genetic lesions required differ from one tumor to another. The likelihood of any given clone of cells accumulating a sufficient number of relevant genetic lesions to give rise to a lymphoma is probably a function of its life span. Prolonged survival of a cell clone may be mediated by viral genomes (e.g., Epstein-Barr virus and human T-cell leukemia/lymphoma virus type 1), by the abnormal expression of cellular genes that inhibit apoptosis (e.g., bcl-2), or by the mutation or deletion of cellular genes that are necessary for apoptosis, e.g., p53. The background rate at which genetic lesions occur is amplified by the interaction of inherited and environmental factors, the latter appearing to be the major determinant of incidence rates. However, inherited factors that influence lymphomagenesis, including variability in the ability to repair DNA damage or in the fidelity of antigen receptor recombinases for their signal sequences, may be crucial determinants of which particular individuals in a given environmental setting develop lymphoma.
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PMID:Molecular basis of lymphomagenesis. 139 68

A high frequency of lymphoma in human immunodeficiency virus-infected individuals has been reported since the outbreak of the acquired immunodeficiency syndrome (AIDS) epidemic in 1982. In the vast majority of cases, these lymphomas are highly aggressive B-cell, non-Hodgkin's lymphoma of intermediate or high grade of malignancy. AIDS-associated non-Hodgkin's lymphoma are histologically classified as small noncleaved cell lymphoma, large cell immunoblastic plasmacytoid lymphoma, or large noncleaved cell lymphoma. Host factors predisposing to lymphoma development in AIDS patients include decreased immunosurveillance as well as human immunodeficiency virus-induced chronic perturbation of the immune system leading to cytokine overproduction and increased B-cell stimulation. These alterations are associated with the development of multiple oligoclonal B-cell expansions, which are characterized by persistent generalized lymphadenopathy. The presence of Epstein-Barr virus within a persistent generalized lymphadenopathy clone further increases the risk of its neoplastic transformation. The appearance of non-Hodgkin's lymphoma is characterized by the presence of a monoclonal B-cell population displaying several genetic lesions, including monoclonal Epstein-Barr virus infection, c-myc rearrangements, Ras mutations, and p53 inactivation. The number and type of lesions varies among the different types of AIDS-non-Hodgkin's lymphoma, defining multiple alternative molecular pathways in AIDS-associated lymphomagenesis.
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PMID:Biologic aspects of human immunodeficiency virus-related lymphoma. 145 5

To study the oncogenesis of human esophageal carcinoma, the presence of DNA sequences homologous to several DNA tumor viruses and the expression of oncogenes and growth factor genes were examined in two esophageal carcinoma cell lines of Chinese origin, CE48T/VGH and CE81T/VGH. Southern blot analyses failed to detect sequences homologous to hepatitis B virus (HBV), Epstein-Barr virus (EBV), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV) or human papilloma virus (HPV) genomes. Northern blot analyses revealed that c-myc, c-src, c-H-ras, c-abl, c-sis, and p53 genes were expressed. In addition, transcripts of transforming growth factor alpha (TGF alpha), TGF beta, and platelet derived growth factor A (PDGF A) genes were detected. These studies suggest that DNA tumor viruses may not be involved in the carcinogenesis of esophageal carcinoma. However, cooperation among different oncogenes and the production of growth factors may play an important role in that carcinogenesis.
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PMID:Absence of genomes of DNA tumor viruses and expression of oncogenes and growth factors in two esophageal carcinoma cell lines of Chinese origin. 147 73

Alterations in the p53 tumor suppressor gene and Epstein-Barr virus status were investigated in 15 nasopharyngeal carcinoma (NPC) biopsies, 4 xenografts, and 2 cell lines from the Cantonese region of southern China. One other established NPC cell line obtained from a northern Chinese patient was also studied. Restriction fragment length polymorphism analysis revealed a loss of heterozygosity for chromosome 17p, where the p53 gene resides, in only one of 15 NPC biopsies. Polymerase chain reaction-single-stranded conformational polymorphism analysis and direct sequencing failed to detect sequence alterations in exons 5 through 8 of the p53 gene in the 15 tumors and in the 4 NPC xenografts, all of which tested positive for Epstein-Barr virus. In contrast, the 3 NPC cell lines were all negative for Epstein-Barr virus and contained G----C transversions in the p53 gene, with cell lines CNE-1 and CNE-2 harboring identical AGA (arginine) to ACA (threonine) changes at codon 280. These results suggest that p53 inactivation is not a necessary component of nasopharyngeal carcinogenesis in Cantonese but may be important in the establishment of cell lines derived from these tumors.
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PMID:Absence of p53 gene mutations in primary nasopharyngeal carcinomas. 151 42

The last decade has seen major advances in the acquisition of knowledge concerning both the cellular and molecular genetics of multiple myeloma. Although discrete and specific changes associated with the plasma cell disorders have yet to be identified, a pattern is emerging that one can associate with the plasma cell disorders. This pattern includes the frequent involvement of chromosomes 1 and 14, and in particular presence of the 14q+ abnormality. But in addition there are typically many other numeric and/or structural changes that can, in fact, involve almost any chromosome, but particularly chromosomes 3, 5, 6, and 7, as well as 11, 14, 17, and 18. The presence of one or more unidentified marker chromosomes is also a typical feature. The ongoing challenges include identification of a crucial initial genetic change (if such exists) as well as the factors contributing to the ongoing karyotypic evaluation that results in complex karyotypes in patients with advanced disease. There is no doubt that the complex karyotypic picture contributes to the major heterogeneity of plasma cells that occurs in malignant plasma cell disorders. Karyotypic complexity underlies heterogeneity in cell morphology, surface antigen expression, response to cytokines, and a variety of other functional characteristics. The aberrant expression of antigens normally found on other hematopoietic progenitors has led to speculation about the true nature of the stem cell in myeloma. The overriding challenge, however, is to fully understand the plasma cell disorders at the molecular level. Although changes have already been noted in the functions of C-myc, the ras family of oncogenes, Bcl-2 expression, and several so called anti-oncogenes such as p53, it is likely that we have only begun to scratch the surface in the area of molecular changes. The potential for involvement at multiple molecular sites and the possibility of complex interactions between gene segments is truly overwhelming. However, it is hoped that at the molecular level a pattern will ultimately emerge. It is most interesting, as previously discussed, that there is an interplay among C-myc, N-ras, Bcl-2, and the Epstein-Barr virus in the predilection for a plasma cell phenotype. Undoubtedly there is much more to learn, and it is truly exciting to finally have some tools and probes at hand to more effectively study the genome in multiple myeloma and related disorders.
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PMID:Cellular and molecular genetic features of myeloma and related disorders. 158 85

Chronically immunosuppressed individuals are susceptible to lymphoreticular tumors. Up to 15% of patients with congenital deficiencies such as ataxia=telangiectasia may develop malignancies, mainly high-grade B cell non=Hodgkin's lymphomas (NHLs). AIDS lymphomas are comprised of NHLs including Burkitt's lymphoma (BL) and primary cerebral lymphomas (PCLs). Almost 3% of all AIDS patients (2824 of 97,258 cases) developed NHL. Epstein-Barr virus (EBV) as a co-factor in AIDS lymphomagenesis has been studied: in 12 cases of 24 AIDS lymphomas EBV by DNA in situ hybridization was found. In an analysis of 6 primary cerebral lymphomas, .5 were positive for EBV DNA by Southern blotting. In Burkitt's lymphoma the characteristic genetic alteration affects the c-myc oncogene. In 1/3 of BL p53 mutations were found but none in the 43 NHLs suggesting that p53 mutations and c-myc activation act synergistically in the pathogenesis of these tumors. Cytotoxic agents dideoxyinosine, dideoxycytosine, and zidovudine may cause secondary neoplasia. 8 of 55 AIDS patients under zidovudine treatment developed high-grade lymphoma 23.8 months subsequently; recently doses were reduced. PCL was found in 21 of 90 patients. A 5.2 months survival was associated with combined treatment with cyclophosphamide, Oncovin (vincristine), methotrexate, etoposide, and cytosine arabinoside compared with 11.3 months with chemotherapy. Colony-stimulating factors (CSFs) alleviate drug-induced myelotoxicity and zidovudine-induced neutropenia, however, l8 of 11 patients receiving granulocyte-macrophage CSF developed hematological toxicity. Interleukine-2 produced by T-helper cells enhancing tumor cells cytotoxicity has been used in AIDS-associated cryptosporidial diarrhea and in 4 patients with AIDS lymphoma with modest response, but its stimulation of the HIV-infected substrate may increase viral proliferation.
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PMID:AIDS lymphomas. 161 63


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