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 most common tumour suppressor gene altered in human cancers is p53, which is located on the short arm of chromosome 17. Structural abnormalities of the short arm and loss of chromosome 17 have been reported to confer resistance to chemotherapy in patients with non-Hodgkin's lymphoma (NHL). Therefore we studied the incidence and prognostic value of p53 deletions in patients with NHL by fluorescence in-situ hybridization using a 40 kb cosmid probe. Specimens obtained from 79 patients with NHL were studied. 46 patients were untreated, and 33 were previously treated. 40 tumours had indolent and 39 had aggressive histologies. p53 deletions were observed in 14 specimens (18%) in 32-90% of the cells. No statistically significant difference in the incidence of p53 deletion was observed between indolent and aggressive NHLs or between untreated and previously treated patients. However, p53 deletions were observed in three of four patients with transformed lymphoma. In the untreated patients, p53 deletion had no effect on response to therapy, time to treatment failure, or survival. We conclude that p53 deletions are uncommon in NHL, and may be frequent in patients with transformed lymphoma. In this study, p53 deletions did not influence treatment outcome or prognosis of NHL. Because monosomy 17 and 17p abnormalities have been reported to confer poor prognosis in NHL, other tumour suppressor genes on 17p should therefore be studied.
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PMID:Analysis of p53 gene deletions in patients with non-Hodgkin's lymphoma by dual-colour fluorescence in-situ hybridization. 932 89

AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL) includes Burkitt's lymphoma (BL) and high-grade B-cell Burkitt-like lymphoma (BLL). Due to the marked polymorphism of AIDS-related non-Hodgkin's lymphomas (AIDS-NHL), the morphologic distinction between these two types of lymphomas is frequently controversial, although it may bear clinical relevance. Although the molecular features of AIDS-BL have been clarified to a certain extent, the genetic peculiarities of AIDS-BLL have not been investigated in detail. In this study we have compared morphologic and genetic features of AIDS-BL and AIDS-BLL in a blind coded fashion. Molecular studies were focused on the genetic lesions known to be implicated in AIDS-NHL, including alterations of c-MYC, BCL-6, p53, deletions of 6q, as well as infection by EBV and HHV-8. Alterations of c-MYC occurred in 10/10 AIDS-BL, whereas they were restricted to 2/10 AIDS-BLL (P < 0.01). Mutations of p53 were present in 5/10 AIDS-BL, whereas they were consistently absent among AIDS-BLL (n = 10; P < 0.05). Infection by EBV occurred in 30% of both AIDS-BL and AIDS-BLL. Rearrangements of BCL-6, deletions of 6q and infection by HHV-8 scored consistently negative in both AIDS-BL and AIDS-BLL. Based on the genetic lesions tested, the molecular profile of AIDS-BLL appears to be closer to that of AIDS-related diffuse large cell lymphoma (AIDS-DLCL) than to that of AIDS-BL. In contrast to AIDS-BLL however, AIDS-DLCL carried rearrangements of BCL-6 in a fraction of cases (2/9). This study, the largest of its kind reported so far, suggests that AIDS-BL and AIDS-BLL have a different molecular pathogenesis and that characterization of genetic lesions may help to distinguish between these two lymphomas.
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PMID:Genetic heterogeneity of AIDS-related small non-cleaved cell lymphoma. 933 31

Recent studies have shown bcl-2 to be regulated by p53. Other studies have suggested an inverse relationship between p53 and bcl-2 protein expression in breast and colonic cancers and in a variety of subtypes of non-Hodgkin's lymphoma. This study investigates the relationship between bcl-2 and p53 protein expression and the correlation between these findings and the grade and cell type of follicular lymphomas according to the REAL classification. Paraffin-embedded nodal follicular lymphomas (n = 37) were subjected to bcl-2 and p53 immunohistochemistry on tissue sections using a three-step ABC system. Positive immunostaining for both oncoproteins was scored using a three-tiered scale: +, < 10 per cent cells; ++, 10-50 per cent cells; and ++(+), > 50 per cent cells (< 10 per cent was used as a cut-off to define negative tumours). Ninety-seven per cent (36/37) of follicular lymphomas expressed bcl-2 protein in all three grades, manifesting in the small cell (grade 1) through to the large cell (grade 3). p53 protein expression showed a pattern of increasing immunostaining with progression towards the high-grade follicular lymphoma: grade 1 = 6 per cent (1/16); grade 2 = 48 per cent (10/21); grade 3 = 100 per cent (6/6). Five cases comprised varying combinations of grades. This latter finding suggests a role for p53 mutation in the progression/transformation of follicular lymphoma. The mechanism, however, differs from that suggested in breast and colonic cancers, since an inverse relationship between bcl-2 and p53 was not demonstrated in the present study.
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PMID:bcl-2 and p53 protein expression in follicular lymphoma. 934 33

In the biology of a cell, the central role of p53 in controlling functions such as G1/S transition (check point) and DNA damage repair, and as a trigger of apoptosis, is well established. Somatic mutations or other changes in P53 have been reported in numerous tumor types, and in some of these, they are associated with poor prognosis. In this study, we examined 237 cytogenetically characterized B-cell non-Hodgkin's lymphomas (B-NHLs) for somatic changes in P53 by Southern blot analysis, by single-strand conformation polymorphism analysis (SSCP) of exon 5 through 9, and by direct sequencing of SSCP variants to determine the frequency and types of mutations and their clinical significance. In a portion of these (173 tumors), we also studied p53 expression by immunostaining. On Southern blots, no gross change was identified in P53 and no mutation was identified in exon 9. In exons 5 through 8, 27 different mutations were identified in 25 patients (23 single-base substitutions, 3 deletions, 1 duplication). Mutations in P53 were identified in 25 of 237 tumors (10.5%), which included 1 of 45 small lymphocytic lymphomas (SLLs), 2 of 38 follicular small cleaved-cell lymphomas (FSCCs), 2 of 35 follicular mixed small cleaved-cell and large-cell lymphomas (FMxs), 1 of 4 follicular large-cell lymphomas (FLCs), 1 of 14 diffuse small cleaved-cell lymphomas (DSCCs), 2 of 17 diffuse mixed small- and large-cell lymphomas (DMxs), and 16 of 84 diffuse large-cell lymphomas (DLCCs); the difference between the histologic groups was significant (P < .01). Among mantle-cell lymphoma (MC) patients, 3 of 10 had mutations. In 16 patients, the mutation was identified in specimens obtained at diagnosis. Mutation of transition type and transversion type occurred at a relative frequency of 2:1. Thirty percent occurred at CpG dinucleotide sequences and the codon for arginine was most frequently affected. Nineteen of 99 tumors with complex cytogenetic abnormalities, but none of 69 tumors with simple cytogenetic abnormalities, had mutations (P < .001). Similarly, 11 of 25 tumors with an abnormality of 17p and 8 of 143 tumors with apparently normal 17p had mutations (P < .0001). Positive correlations were found between a mutation and p53 expression (P < .001), between missense type mutations and p53 expression (P < .005), and between 17p abnormalities and p53 expression (P < .05). Twenty-two of 49 patients without mutation and 14 of 17 patients with mutations died (P < .05), but there was no significant difference in median survival. Similarly, 21 of 26 p53 positive patients died, whereas only 1 of 24 p53-negative patients died on-study (P < .001). Among p53-negative patients, mutation (P < .01) was positively associated with a fatal outcome. These findings indicate that in B-NHL, somatic changes in P53 were present in diagnostic specimens of all histologic types, but at a higher frequency in DLC and MC tumors. P53 mutation and/or expression has a negative influence on survival, and therefore can serve as prognostic indicators. Immunostaining for p53 is an effective way to screen for P53 changes in these tumors.
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PMID:Correlation between mutation in P53, p53 expression, cytogenetics, histologic type, and survival in patients with B-cell non-Hodgkin's lymphoma. 935 78

We have identified three unbalanced translocations involving chromosomes 5 and 17, der(5)t(5;17), der(17)t(5;17), and dic(5;17), in the malignant cells from 17 patients with myeloid neoplasms. Six patients had a primary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) de novo; ten patients had therapy-related MDS and/or AML (t-MDS/t-AML), and one patient had chronic myelogenous leukemia in myeloid blast phase. Two of the six patients with MDS or AML de novo had extensive exposure to industrial solvents, and one patient had Seckel syndrome. The primary diagnoses for the ten patients with t-MDS/t-AML were breast carcinoma and Hodgkin's disease in two patients each, and non-Hodgkin's lymphoma, multiple myeloma, chronic lymphocytic leukemia, ovarian carcinoma, thyroid carcinoma, and rhabdomyosarcoma in one patient each. Four patients had received both prior chemotherapy and radiotherapy, four others received prior chemotherapy only, and the remaining two patients only prior radiotherapy. Fluorescence in situ hybridization of centromere-specific probes for chromosomes 5 and 17 revealed that a dicentric rearrangement was the most common (13/16 patients examined). The genetic consequences of these chromosomal rearrangements are partial monosomy for 5q and 17p. Two of six patients examined had point mutations in TP53, suggesting that loss of function of TP53 in addition to loss of a tumor suppressor gene on 5q may be involved in the pathogenesis of the malignant disease in some of these patients.
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PMID:dic(5;17): a recurring abnormality in malignant myeloid disorders associated with mutations of TP53. 936 36

The use of RT in pediatric cancer has been virtually eliminated in certain diseases (NHL); greatly reduced in some (Wilms' tumor, ALL, neuroblastoma); and refined and modified in others (rhabdomyosarcoma, Ewing's sarcoma). At present, however, it seems clear that RT will continue to be an important modality (particularly in brain tumors) and a much greater understanding of its effects has been achieved and utilized. The knowledge of the occurrence of late effects and SMN in a child cured of cancer is continuing to modify initial treatment strategies: A classic example of such an effort is the common use of lower RT doses and nonalkylator-based chemotherapy in Hodgkin's disease. Further, the use of DNA testing in children may be able to identify the presence of germline RB and p53 mutations, which may identify a child at high risk for SMN, so that appropriate therapeutic modifications may be made. In addition, knowledge of these late consequences in children mandates that they be carefully monitored and closely followed, so that prompt and effective treatment can be administered to give them a better chance for a long and healthy life.
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PMID:Pediatric radiotherapy. An overview. 937 90

We have recently reported a series of 15 non-villous splenic marginal zone lymphoma patients, six of whom showed p53 mutations (40%). This molecular alteration did not correlate with any particular clinico-pathologic feature at diagnosis. After a median follow-up of 56 months, four cases evolved into aggressive fatal non-Hodgkin's lymphoma (NHL) and two had refractory progressive disease; interestingly, p53 mutations were demonstrated in five of these patients at diagnosis. As the patients with wild-type p53 presented responsive or indolent disease, this genetic alteration may be an early marker of aggressive transformation or refractoriness. p53 evaluation at diagnosis could be advisable in this particular subset of NHL.
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PMID:Poor prognosis in non-villous splenic marginal zone cell lymphoma is associated with p53 mutations. 937 58

Myelodysplastic syndrome (MDS) is an uncommon but serious complication of patients who undergo autologous bone marrow transplantation (auto-BMT) for non-Hodgkin's lymphoma or Hodgkin's disease. Some patients exhibit an indolent course, but others succumb to aggressive disease. p53 overexpression is rare in de novo MDS but common in therapy-associated MDS. We used an immunostaining method to analyze expression of p53, the p53-associated tumor suppressor gene products, MDM2, p21waf1, retinoblastoma gene protein (pRB), and the antiapoptotic oncoprotein bcl-2 before and after BMT in BM specimens from eight patients with clonal karyotypic abnormalities characteristic of MDS. Staining was compared with findings in normal BM specimens and specimens from auto-BMT controls and patients with de novo MDS. p53 protein was found in three (75%) of four post-transplantation specimens from patients in whom a clinically aggressive form of MDS developed. In contrast, p53 was absent in all of the specimens from four patients with karyotypic evidence of MDS, but with indolent disease. bcl-2 protein was overexpressed by immature myeloid cells in seven of eight pre-BMT specimens. After BMT, it was predominantly found at low levels in cases positive for p53. MDM2 was present only after transplantation and was found with equal frequency in patients with indolent and aggressive MDS. We detected p21waf1 in only one aggressive post-BMT MDS specimen. pRB was normally expressed in all of the specimens. These data show that p53 and bcl-2 staining patterns in post-transplantation MDS are similar to those described in therapy-associated MDS. p53 positivity is associated with poor prognosis in auto-BMT patients with MDS. Expression of MDM2, p21waf1, and pRB in this group of patients is not helpful in predicting outcome.
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PMID:Expression of p53, MDM2, p21waf1, bcl-2, and retinoblastoma gene proteins in myelodysplastic syndrome after autologous bone marrow transplantation for lymphoma. 938 63

In several types of solid tumours, circulating antibodies to p53 are seen in about a third of cases with a p53 mutation, but are absent in cases without p53 mutation. Therefore detection of those antibodies has relatively low sensitivity but high specificity in the detection of p53 mutations. We looked for circulating p53 antibodies by ELISA in 56 adult non-Hodgkin's lymphoma (NHL) and 80 multiple myeloma cases. A certain or highly probable p53 mutation was found by SSCP analysis, immunocyto- or immunohistochemistry in 8/35 (23%) NHL cases and 2/19 (10%) MM cases analysed by these techniques. None of the 80 MM cases and only one of the 56 cases of NHL had circulating p53 antibodies. The positive case had Burkitt's lymphoma and a p53 missense mutation at codon 273. Thus, very few MM and NHL patients with a p53 mutation develop p53 antibodies and this test does not appear to be useful in haematological malignancies.
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PMID:Very low incidence of p53 antibodies in adult non-Hodgkin's lymphoma and multiple myeloma. 945 Aug 8

A high incidence of non-Hodgkin's lymphoma of the pleural cavity has developed in Japanese patients with long-standing pyothorax (38 years on average) resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. Patients with pyothorax-associated lymphoma (PAL) have long been exposed to antituberculous drugs, antibiotics, bacterial or viral products, and frequent diagnostic radiation for the confirmation of pneumothorax and pyothorax. We analyzed p53 mutations on paraffin-embedded specimens from 21 patients with PAL by PCR-single-strand conformational polymorphism followed by direct sequencing. An unusually high frequency of p53 mutations (14 of 21 cases, 67%) was detected in the PAL specimens, and mutations consisted of 13 nucleotide substitutions and 1 deletion. Furthermore, 10 of 13 substitutions (77%) occurred at dipyrimidine sites (CC:GG to CT:GA substitution). Such specificity has not been reported, except for solar light-related skin cancer and AIDS-related lymphoma in some parts. An UV light mimetic agent may be produced in the long history of chronic inflammation in tuberculosis or immunodeficient patients.
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PMID:Frequent p53 mutations at dipyrimidine sites in patients with pyothorax-associated lymphoma. 951 88


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