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)

The data presented here indicate that the pathogenesis of AIDS-NHL is variably associated with multiple genetic alterations including monoclonal EBV infection, oncogene activation (c-myc, N-, Ki-ras) and tumor suppressor gene (p53) inactivation. Up to three (3 cases) or four (1 case) different lesions have been observed in the same tumor. The distribution of these lesions among the various histotypes is heterogeneous, although some preferential associations have been found either between lesion and histotype or between lesions. The most notable case involves p53 mutations/loss that is exclusively associated with the SNCC lymphoma subtype. Since alterations of the c-myc gene occur at very high frequency in this same histotype it is possible that both lesions may be required for the pathogenesis of the BL phenotype. The consistent negativity of p53 lesions in other NHLs associated or non associated with HIV infection (18) reinforces this hypothesis. Finally, we note that the frequency of p53 mutations is significantly higher in AIDS-BL than in non HIV-related BL (18), although the significancy of this difference remains to be assessed. This study confirms the relatively low frequency of EBV infection in systemic AIDS-NHL in general, but reinforces the notion that EBV may be required for the pathogenesis of AIDS-LC-IBP, as recently suggested by the high frequency of EBV positivity in primary CNS AIDS-NHL which are mostly represented by LC-IBP (2). Conversely, the low frequency of EBV sequences in the AIDS-SNCC lymphomas appears similar to that observed in sBL. Only in a small minority of cases were ras oncogene mutations found, mostly associated with the BL type.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular pathogenesis of HIV-associated lymphomas. 132 69

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

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

Using immunofluorescence technique we have analysed the Rb, p53, EBNA-2 and EBNA-5 expression pattern in EBV infected human B-cells and established lymphoblastoid cell lines (LCL-s). Resting B-cells showed only a faint Rb and no p53 immunostaining. The expression of both Rb and p53 increased after EBV infection. The change was first detectable 6 h after infection. The frequency of brilliantly Rb positive cells increased more rapidly than p53 positives. EBNA-2 and EBNA-5 became first detectable 12 h after infection. The frequency of EBNA positive cells in the freshly infected cultures was concordant with the proportion of CD23 and PCNA positives, but remained consistently below the frequency of Rb and p53 positive cells. Double immunofluorescence staining showed that all EBNA-5 positive cells were strongly Rb and p53 positive. LCL-s did not stain for p53, whereas the Rb staining was maintained at a high level. The EBNA-5 staining pattern changed from brilliant almost homogeneous nuclear staining in the freshly infected B-cells, to a nonhomogeneous pattern with a small number of strongly fluorescent nuclear bodies in established LCL-s. There was no change in the EBNA-2 staining pattern. Our findings indicate that the immortalization of B-cells by EBV may initially involve a high expression of EBNA-5, p53 and Rb, but only cells with low p53 and focal expression of EBNA-5 in nuclear bodies have the selective advantage required to grow into immortalized lines.
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PMID:Resting B-cells, EBV-infected B-blasts and established lymphoblastoid cell lines differ in their Rb, p53 and EBNA-5 expression patterns. 775 63

The neoplastic nature of Hodgkin's disease (HD) is suggested by several lines of evidence, including aggressive clinical course, presence of proliferating atypical cells morphologically recognized as Hodgkin's and Reed-Sternberg cells (H-RS), aneuploidy, and, in the minority of cases, clonality. Nevertheless, the etiopathogenesis of HD still remains elusive, and probably diverse. This uncertainty is partly due to the peculiar histology of HD lesions, characterised by the paucity of the putative neoplastic cell component, i.e. H-RS cells, admixed to a variety of reactive cells which prevent an exhaustive investigation at molecular level. Nevertheless, the possible involvement of different molecules with oncogenic potential has been recently suggested on the basis of immunohistological and molecular biology studies. These include oncogenes such as bcl-2 and MDM2 and anti-oncogenes such as p53. In addition, a large amount of data has accumulated on the possible role of EBV infection in HD. The colonization of lymphoid tissues by immortalized H-RS cells can account for the derangement of cytokine networks leading to microenvironmental and systemic abnormalities. In addition, a variety of soluble receptors (sIL-2R, sCD30, sTNF-R), and adhesion molecules (sICAM-1) are abnormally produced at sites of disease involvement. Some of these molecules still retain the ability to bind their ligands and can potentially contribute to the derangement of immune mechanisms observed in HD. Many of these soluble molecules can also be found in the patient's sera providing new potential prognostic and follow-up parameters in HD patients. The comparative analysis of the same molecules within the tissue, using immunohistochemistry, and in the blood, using immunochemical assays, appears as a promising informative approach.
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PMID:Biopathologic features of Hodgkin's disease. 778 48

We investigated 34 cases of T-cell neoplasm [15 cases of T-cell granular lymphocytic leukemia (T-GLL), 10 cases of T-cell non-Hodgkin's lymphoma (T-NHL), six cases of T-cell chronic lymphocytic leukemia (T-CLL), and three cases of cutaneous T-cell lymphoma] to study their association with Epstein-Barr virus (EBV). In 4 (three T-NHL and one T-GLL) of 34 cases, EBV genome was detected in a single episomal form, while polyclonal EBV-DNA was detected in one (T-NHL) of the remaining cases. All three cases of T-NHL having monoclonal EBV episome showed histologically diffuse large-cell lymphoma and developed leukemic conversion. Phenotypic analysis showed that two of these four cases were CD4+, CD8-, and the remaining two cases were CD4-, CD8+. The cells from all four cases were confirmed to be in T-cell lineage by detecting the rearrangement of T-cell receptor (TCR) beta or gamma chain gene. By reverse transcription-polymerase chain reaction (RT-PCR), EBNA-1 was detected at low levels, and neither EBNA-2 nor LMP-1 were found in any of the three cases examined. Lack of the expression of EBNA-2 and LMP-1 was also confirmed by immunocytochemical staining. The cells of these four cases did not show rearrangement or overexpression of c-myc and bcl-2 genes by Southern and Northern blots, and the mutation of p53 gene was detected in only one patient. These results suggest that other latent gene products of EBV or other cellular oncogenes are involved in the development of Japanese T-cell neoplasm after EBV infection.
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PMID:Lack of the expression of EBNA-2 and LMP-1 in T-cell neoplasms possessing Epstein-Barr virus. 781 2

The posttransplantation lymphoproliferative disorders (PT-LPDs) are a morphologically heterogeneous group of Epstein-Barr virus (EBV)-driven lymphoid proliferations of varying clonal composition. Some PT-LPDs regress after a reduction in immunosuppression, while others progress in spite of aggressive therapy. Previously defined morphologic categories do not correlate with clonality, and neither morphology nor clonality has reliably predicted the clinical behavior of PT-LPDs. We investigated 28 PT-LPD lesions occurring in 22 patients for activating alterations involving the bcl-1, bcl-2, c-myc, and H-, K- and N-ras proto-oncogenes and for mutations involving the p53 tumor suppressor gene. We correlated the results of these studies with the morphology of the lesions, their clonality based on Ig heavy and light chain gene rearrangement analysis, and the presence and clonality of EBV infection. We found that the PT-LPDs are divisible into three distinct categories as follows: (1) plasmacytic hyperplasia: most commonly arise in the oropharynx or lymph nodes, are nearly always polyclonal, usually contain multiple EBV infection events or only a minor cell population infected by a single form of EBV, and lack oncogene and tumor suppressor gene alterations; (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma: may arise in lymph nodes or various extranodal sites, are nearly always monoclonal, usually contain a single form of EBV, and lack oncogene and tumor suppressor gene alterations; and (3) immunoblastic lymphoma or multiple myeloma: present with widely disseminated disease, are monoclonal, contain a single form of EBV, and contain alterations of one or more oncogene or tumor suppressor genes (N-ras gene codon 61 point mutation, p53 gene mutation, or c-myc gene rearrangement). The PT-LPDs are divisible into three categories exhibiting distinct morphologic and molecular genetic characteristics. Alterations involving the N-ras and c-myc proto-oncogenes and the p53 tumor suppressor gene may play an important role in the development and/or progression of the PT-LPDs.
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PMID:Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders. 781 11

Lymphoma is one of the defining manifestations of AIDS. Most of these lymphoproliferations are high-grade B-cell non-Hodgkin's lymphoma. Unlike lymphoproliferations that arise in other settings of immunodeficiency, HIV-related lymphomas have a variable association with Epstein-Barr virus (EBV) and also contain alterations in c-myc and p53. EBV infection appears to precede clonal expansion, and its latent expression pattern (Epstein-Barr nuclear antigen1+/Epstein Barr nuclear antigen 2-/latent membrane protein+) is unique among non-Hodgkin's lymphomas. Both EBV types A and B are present in HIV-related lymphomas. Mutations in c-myc include translocations and point mutations. Other altered loci include ras and bcl-6. Although all of these somatic alterations can be detected in lymphomas arising in the general population, their accumulation in a relatively short period (6 to 8 years) after HIV infection suggests an acceleration of underlying mechanisms.
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PMID:Biologic aspects of AIDS-related lymphoma. 782 54

Tumor biopsies obtained from 25 Saudi Arab patients with nasopharyngeal carcinoma (NPC) were examined for the presence of Epstein-Barr virus (EBV) DNA detected by the polymerase chain reaction (PCR) and for the incidence of p53 mutations screened by a combination of PCR, single strand conformation polymorphism (SSCP) and PCR-restriction fragment length polymorphism (PCR-RFLP). DNA sequencing was carried out to confirm the occurrence of p53 mutation. While 92% of the tumor specimens were found to carry EBV DNA, only 1/25 showed the incidence of a homozygous mutation at codon 248 of the p53 gene. The data showed that despite a high association of EBV infection with Saudi NPC, the frequency of p53 mutations was very low. Our results are consistent with the worldwide observation of infrequent p53 mutations in NPC.
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PMID:A molecular study of EBV DNA and p53 mutations in nasopharyngeal carcinoma of Saudi Arab patients. 791 50

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. AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) is almost invariably derived from B cells and is classified as high- or intermediate-grade NHL, according to the working formulation. Two main histologic types are recognized, including small noncleaved cell lymphoma (SNCCL) and diffuse large cell lymphoma (DLCL). Pre-existing host factors putatively involved in lymphoma development include disrupted immunosurveillance, deregulated cytokine production, chronic antigen stimulation, and infection by Epstein-Barr virus (EBV). These alterations are associated with the development of multiple oligoclonal expansions which correspond to the clinical phase known as persistent generalized lymphadenopathy (PGL). The appearance of a true AIDS-NHL is characterized by the presence of a monoclonal B-cell population displaying several genetic lesions, including monoclonal EBV infection, c-MYC and BCL-6 rearrangements, RAS mutations, p53 inactivation, and 6q deletions. These genetic lesions cluster into two distinct molecular pathways, which specifically associate with the different histologic subtypes of AIDS-NHL, i.e., AIDS-SNCCL and AIDS-DLCL. The presence of distinct genetic pathways for AIDS-SNCCL and AIDS-DLCL correlate with a number of clinical features which distinguish these two groups of tumors, including differences in the age of onset, CD4 counts at the time of presentation, time elapsed since HIV infection, and clinical outcome.
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PMID:Molecular pathology of AIDS-related lymphomas. Biologic aspects and clinicopathologic heterogeneity. 799 35


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