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)

Gastric MALT lymphomas are clinically and histologically quite distinct from comparable low-grade B-cell lymphomas of lymph nodes. Their histology suggests that immunological mechanisms might be operative in their growth. Given that there is normally no lymphoid tissue in gastric mucosa and that Helicobacter pylori (H. pylori), the only common bacterial antigen in the stomach, results in the accumulation of gastric MALT, the possibility that this organism is implicated in the pathogenesis of gastric lymphoma has been extensively investigated. It appears that most, but not necessarily all, gastric MALT lymphomas arise in MALT acquired in response to H. pylori infection and develop by stepwise accumulation of genetic abnormalities. Early molecular events in the evolution of gastric MALT lymphoma from 'acquired' MALT include trisomy 3, t(11;18)(q21;q21), genetic damage leading to genetic instability, as indicated by the so-called replication error repair (RER) phenotype, and both p53 and c-myc mutations. At this stage in their development, the growth of the lymphomas is driven by contact between the neoplastic B cells and H. pylori specific intra-tumoral T cells. Eradication of H. pylori causes the tumour to enter a latent phase resulting in clinical regression. Later events, such as t(1;14)(p22;q32), appear to be linked to a capacity for autonomous growth, loss of sensitivity to H. pylori and dissemination of the lymphoma beyond the stomach and gastric lymph nodes. Cloning of the breakpoint in t(1;14) has allowed the identification of a new tumour suppresser gene, bc110. High grade transformation of MALT lymphoma has been associated with p53 inactivation, deletions of p16 and t(8;14).
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PMID:Gastric MALT lymphoma: from concept to cure. 1044 84

B-cell chronic lymphocytic leukaemia (B-CLL) results from the clonal expansion of mature B lymphocytes. The detection of leukaemia-associated genetic markers in CD34-positive progenitor cells in a subset of B-CLL patients suggests that malignant transformation in B-CLL occurs in an immature progenitor cell compartment. To further quantify the percentage of B-CLL patients with genetically aberrant progenitor cells we have investigated CD34+ bone marrow cells in 11 B-CLL patients at the single cell level by simultaneous genetic and immunophenotypic analysis (FICTION). In five patients with trisomy 12, CD34+ haemopoietic progenitor cells were detectable on bone marrow smears. In one patient with trisomy 12, CD34+ progenitor cells were isolated by FACS sorting. In all six patients trisomy 12 was not found in the CD34+ cells. Progenitor cells were also analysed in three patients with Rb-deletion and in two patients with deletion of p53. In all patients the genetic marker was not detected in the CD34+ cells. In conclusion, we did not find genetically aberrant progenitor cells in this group of B-CLL patients. These results suggest that the subset of B-CLL patients with genetically aberrant CD34+ cells may be very small. This is of significance for our understanding of B-CLL biology and for future strategies using autologous stem cell transplantation.
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PMID:Analysis of progenitor cell involvement in B-CLL by simultaneous immunophenotypic and genotypic analysis at the single cell level. 1055 6

Indolent lymphomas are a markedly heterogeneous group of lymphoproliferative disorders including B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, follicular lymphoma, mantle cell lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma. The molecular pathophysiology of indolent lymphoma is characterized by distinct genetic pathways which selectively associate with different clinico-pathologic categories of the disease. At diagnosis, B-cell chronic lymphocytic leukemia frequently display deletions of 13q14, trisomy 12 and alterations of the ATM gene, whereas evolution to Richter's syndrome is associated with disruption of p53. Lymphoplasmacytoid lymphoma carries t(9;14) (p13;q32) in approximately 50% of cases, leading to the deregulated expression of the PAX-5 gene. Follicular lymphoma consistently harbors rearrangement of BCL-2. With time, a fraction of follicular lymphoma accumulates mutations of p53 and of p16 and evolves into a high grade lymphoma. MALT-lymphoma frequently associates with alterations of API2/MLT and, in some cases, of p53, BCL-6 and BCL-10. Studies of genotypic and phenotypic markers of histogenesis have shown that mantle cell lymphoma and a fraction of B-CLL/SLL derive from naive B-cells, whereas follicular lymphoma, lymphoplasmacytoid lymphoma and MALT-lymphoma originate from germinal center (GC) or post-GC B-cells. The identification of distinct genetic categories of indolent lymphoma may help in the therapeutic stratification of these disorders. In addition, genetic lesions of indolent lymphoma provide useful molecular markers for disease monitoring by high sensitivity techniques.
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PMID:Molecular pathophysiology of indolent lymphoma. 1068 15

Various genetic abnormalities are often found in B-CLL, but their relative importance in the pathogenesis and evolution of the disease has not been adequately clarified. We studied the expression of bcl-2 protein and the possible simultaneous occurrence of bcl-2 overexpression, trisomy 12 and the Rb1 and p53 gene deletions in 38 patients with B-CLL by combining immunophenotyping and dual color interphase FISH. We also looked for correlation between the genetic abnormalities and clinical parameters such as stage, disease duration from diagnosis to the time of study and overall survival. High expression of the bcl-2 protein was found in 76.3% of the patients (29/38). Trisomy 12 was found in 37% of cases (14/38) and Rb1 monoallelic gene deletion in 42% (16/38). The percentage of cells with hemizygous Rb1 deletion ranged from 13 to 18%. Monoallelic deletion of p53 was found in 29% of cases (11/38). The number of cells with only one signal ranged from 28 to 98%. Patients in stage A had on average, less than one abnormality, while patients in stage C had 2.6 abnormalities. Patients appeared to accumulate genetic abnormalities with time. Bcl-2 overexpression was found early in the course of the disease. Trisomy 12 appeared later, at about the same time as Rb1 deletion, but was not associated with adverse prognosis. Monoallelic deletion of p53 gene appeared rather late in the course of the disease and was associated with advanced stage. Despite the fact that more deaths occurred in the group of patients with three or four abnormalities and the presence of p53 gene deletion, differences in survival were not statistically significant, probably due to the limited number of patients in each group. A larger group of patients studied in a prospective manner will better clarify these issues in the future.
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PMID:Simultaneous detection of BCL-2 protein, trisomy 12, retinoblastoma and P53 monoallelic gene deletions in B-cell chronic lymphocytic leukemia by fluorescence in situ hybridization (FISH): relation to disease status. 1078 95

Antitumor effect of N-9-[2-(phosphonomethoxy) ethyl]-2,6-diaminopurine (PMEDAP) was studied in an in vivo model of s.c. transplanted Sprague-Dawley (SD/cub) rat T-cell lymphomas. Three individual SD/cub neoplasias (SD10/96, SD14/97, SD1/90) of different phenotypes were used. During the treatment, survival of the rats, increase of lymphoma mass, and DNA fragmentation detected by APO/BRDU kit, as well as Bcl2 and p53 protein expression, were followed. The study gives evidence of the positive therapeutic effect of PMEDAP in two of the three tested lymphomas, SD10/96 and SD14/97. Slowly growing SD1/90 lymphoma differs from the others in a uniform karyotype with trisomy of chromosome 11, CD4- immunophenotype, heterogeneous cellular morphology and constitutive expression of p53 protein found in some neoplastic cells. Thus, the diverse anticancer efficacy of PMEDAP treatment among SD/cub lymphomas could be associated with the different phenotypes of individual neoplasias.
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PMID:Anticancer effect of PMEDAP--monitoring of apoptosis. 1081 Mar 95

Most entities of B-cell malignant non-Hodgkin's lymphomas (NHL) are characterized by typical primary chromosomal changes such as the t(14;18) in follicular lymphoma or the t(11;14) in mantle cell lymphoma. In contrast, marginal zone B-cell lymphomas (MZBL), arising at different nodal and extranodal sites, are poorly characterized on the genetic level. We performed cytogenetic investigations in 20 splenic and in 10 nodal MZBL and analyzed 52 MZBL (including 12 MALT-type lymphomas) for deletions of TP53, D13S25, and RB1 loci by fluorescence in situ hybridization. A new nonrandom chromosomal aberration, del(10)(q22q24), was found as a clonal anomaly in 3 out of 20 cases of splenic MZBL. Further recurring abnormalities such as del(7q) or trisomy 3 were found to be characteristic chromosomal changes in a subset of splenic MZBL. TP53 was deleted in 5/25 cases of splenic MZBL. Deletions involving band 13q14 were only rarely encountered, challenging a previous report that stated a dissociated D13S25-RB1 status as characteristic in splenic MZBL. There are fundamental differences between the different subtypes of marginal zone lymphomas as defined with current classification schemes. Splenic MZBL, in contrast to most other entities of B-cell NHL, seems to constitute a heterogeneous disease especially with regard to genetic alterations. del(10)(q22q24) could be of importance at least in a subset of this lymphoma entity.
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PMID:Marginal zone B-cell lymphomas (MZBL) arising at different sites represent different biological entities. 1086 46

Abnormalities of the TP53 tumor suppressor gene at 17p13.1 are prognostically adverse in a variety of hematolymphoid malignancies. The present study utilized interphase fluorescence in situ hybridization (I-FISH) to detect TP53 deletions and trisomy 12 in 101 clinical specimens from 98 patients with B-cell lymphoproliferative disorders (B-LPDs). Twelve patients had TP53 deletions (group A), 23 had trisomy 12 (group B), and 63 had neither (group C). The groups did not significantly differ in age, duration of disease, absolute lymphocyte count, or percentage with an immunophenotype or cytology atypical for chronic lymphocytic leukemia (CLL). The clinical stage of disease and lactate dehydrogenase (LDH) level were higher in group A, with less response to therapy. After a median follow-up of 19 months, seven of the patients in group A had died of disease (another patient subsequently has had large cell transformation) compared with none in group B and nine in group C. Multivariate analysis found the stage of disease and TP53 deletions as the only parameters independently associated with shortened survival (P < 0.001). Thirty-nine patients had conventional cytogenetic analysis (CCA) which was complexly abnormal in 11 patients; 6 of whom died of disease. There was a trend for complex cytogenetics to be seen more frequently in group A, often with 17p involvement. For most laboratories, CCA may be the preferable initial study to identify prognostically different subgroups of B-LPDs. However, as more probes and clinical outcome data become available, I-FISH will likely play an increasingly important ancillary role.
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PMID:TP53 deletions but not trisomy 12 are adverse in B-cell lymphoproliferative disorders. 1086 51

Sarcomatoid renal cell carcinoma (SRCC) is an aggressive tumor variant thought to arise predominantly from dedifferentiation of clear cell carcinoma. A few reports of SRCC associated with non-clear cell tumors led to the presumption that SRCC may arise from any renal cell carcinoma, although direct evidence of this is lacking. Cytogenetic studies on 3 previously documented SRCCs associated with papillary renal cancers showed either 3p deletions or absence of trisomy 7, 17 in the sarcomatoid tumors, suggesting origin from a coexistent clear cell tumor. The present case represents the first conclusive evidence of direct progression of non-clear cell carcinoma to SRCC with both tumor components containing multiple copies of chromosomes 7 and 17. Many genetic anomalies, including p53 mutations, frequently recognized in SRCC were not recognized in this case, highlighting the importance of cytogenetic evaluation of all SRCC. The patient is well and without evidence of tumor progression 1 year after surgery, and the sinister outlook of SRCC in association with clear cell carcinoma may not apply in SRCC of non-clear cell origin.
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PMID:Sarcomatoid renal cell carcinoma of papillary origin. A case report and cytogenic evaluation. 1110 68

Laryngeal squamous-cell carcinoma is often preceded by pre-malignant lesions. In this study, pre-malignant as well as malignant laryngeal lesions were analyzed using p53 immunohistochemistry and in situ hybridization for chromosomes 1, 7, 9, 17 and 18. Microsatellite analysis was performed on laser-microdissected tissue fragments with the aim of studying loss of heterozygosity (LOH) of 9p21, 17p13 and 18q21. Sequential biopsies were analyzed from a few cases to study genetic progression in more detail. The following genetic progression patterns were observed: (i) histologically normal mucosa and hyperplastic lesions without malignant progression were typically disomic for all chromosomes tested and showed no or only basal cell layer positivity for p53 and no allelic loss; (ii) hyperplastic lesions preceding dysplastic/invasive growth frequently showed trisomy for chromosome 7 and LOH of 9p21 and 17p13, and small foci within these lesions sometimes showed tetraploidization and p53 positivity; (iii) dysplastic lesions were characterized by a tetraploid chromosome content, LOH of 9p21 and 17p13 and p53 positivity; (iv) carcinoma in situ lesions and invasive laryngeal carcinomas showed a more unbalanced chromosome pattern and an additional 18q21 LOH. These results show that different steps in aneuploidization correlate with LOH of 9p21, 17p13 and 18q21 in early laryngeal carcinogenesis. These genomic changes could be of potential use in the diagnosis and prognosis of pre-malignant laryngeal lesions.
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PMID:Specific steps in aneuploidization correlate with loss of heterozygosity of 9p21, 17p13 and 18q21 in the progression of pre-malignant laryngeal lesions. 1114 44

Atherosclerosis is the most frequent cause of death in industrialized countries. Lesions are characterized by lipid deposits, focal thickening of the arterial wall with proliferation of smooth muscle cells (SMC), mononuclear infiltrates and neoformed vessels. In this paper, we studied the proliferative characteristics and cytogenetic alterations of SMC. These cells, expressing specific muscular actin, were diploid with an increased proliferative index for PCNA. A high percentage of SMC showed intense expression of p53. There were signs of chromosomal instability, being the most frequent findings chromosome 7 trisomy and chromosome 11 monosomy. Additionally, the gene for FGF-3 showed a marked amplification. These findings strongly suggest that SMC proliferation is active, and is related to the accumulation or mutation of the p53 oncoprotein. It also presents specific chromosomal alterations in close relation with growth factors. According to these findings SMC hyperplasia in the atherosclerosis plaque may be considered as a cellular clonal expansion.
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PMID:[Proliferative activity and chromosomal alterations of smooth muscle cells in atherosclerosis]. 1118 99


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