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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trisomy of chromosome 12 is one of the commonest cytogenetic abnormalities in the karyotype in chronic lymphocytic leukemia (CLL). It is associated with atypical morphology of lymphocytes, progressing disease and poor survival. A high incidence abnormality in the B-cell CLL is deletion of chromosome 13 (13q14) detected by using modern diagnostic methods such as southern blot hybridization and fluorescence in situ hybridization. It occurs in 51% of the CLL patients and in as much as 70% in mantle-cell lymphoma. The deletion of 13q14.3 affects a locus telomeric to the RB1 gene (retinoblastoma gene) and the marker D13S25 which bear relation to a candidate tumour suppressor gene. Also common are the chromosome 14 abnormalities which are expressed as the translocation t(11;14)(q13;q32) and which correlate with a high leukocytes count, adverse response to cytostatic therapy and increased risk of prolymphocytic proliferation. The oncogene BCL-1 is activated in this translocation. Deletions of the long arm of chromosome 18 (18q21)(q32;q13.1) activate the BCL-2 oncogene, while the translocation t(14;19)(q32;q13.1) activates the BCL-3 oncogene. Essential role in the pathogenesis of CLL is played by the aberrations in chromosome 17 and the p53 mutations (17p13.1). The gene p53 is defined as a tumour suppressor gene; mutations of this gene leads to a CLL characterized with rapid progression, aggressive course, poor prognosis and low survival. The deletions in chromosome 7 are associated with the multidrug resistance gene which causes resistance to doxorubicin, vinblastine and colchicine. All these abnormalities are characteristic of the B-cell chronic lymphocytic leukemia. In the T-cell leukemia characteristic deletions are 11q22-q23, a.14q23.1, as well as the inversion inv(14)(11q32) and some rarer aberrations.
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PMID:Cytogenetic abnormalities in chronic lymphocytic leukemia. 1134 38

Chronic lymphocytic leukemia (CLL) is the most common leukemia in humans, with the major cytogenetic aberrations of trisomy 12 and deletion of 13q14. This study examined the influence of these aberrations on general gene replication. The study group included three subgroups: (1) 15 CLL patients, (2) 4 CLL patients with trisomy 12, (3) 3 CLL patients with deletions in 13q14. Five healthy individuals served as a control group. Monocolor fluorescence in situ hybridization (FISH) with probes for c-myc, HER-2/neu, and p53 was applied to lymphocyte nuclei for the evaluation of replication timing. Asynchronous replication (SD) rate was significantly higher in all CLL patients (P < 0.01) when compared to the control group and was even higher in the group of CLL patients with trisomy 12 and 13q14 deletion (P < 0.01). The asynchrony rate was significantly higher in cells with trisomy 12 for all three probes analyzed, compared to "healthy" cells in the same patients (P < 0.001). To conclude, in CLL patients with a chromosomal aberration such as trisomy 12 and 13q14 deletion we were able to demonstrate a high rate of asynchrony of replication. The high correlation between cells with trisomy 12 and SD pattern could reflect direct influence of the aberration on gene replication and cell cycle control.
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PMID:The influence of cytogenetic aberrations on gene replication in chronic lymphocytic leukemia patients. 1136 50

In this review, we summarize the morphological features and immunophenotypic profile of chronic lymphocytic leukemia (CLL) cells, discuss the value of these investigations as front line diagnostic tests, and emphasize their correlation with the clinical features, disease progression, molecular genetics and pathogenesis of CLL. In CLL, the morphology of the circulating cells is characteristic and typical in the majority of cases. However, 15% of patients, either at diagnosis or during the course of the disease, show atypical morphology reflected by either (1) an increased (> 10%) number of circulating prolymphocytes, designated CLL/PL, or (2) an increased (> 15%) number of circulating lymphoplasmacytic and cleaved cells, designated 'atypical' CLL. There is strong evidence of a close association between atypical morphology (CLL/PL) and atypical (CLL) and clinical features, e.g. disease progression, advanced stage and survival, molecular genetics, particularly trisomy 12, but also the rare cases with t(11;14) or t(14;19), p53 abnormalities, unmutated immunoglobulin (Ig) VH genes and origin of the cell (naive, pregerminal center cell). CLL cells have a distinct immunological repertoire different from that of other lymphoproliferative disorders. The typical CLL phenotype is CD5+, CD23+, FMC7-, weak expression of surface Ig (sIg) and weak or absent expression of membrane CD22 and CD79b. The latter marker identifies an extracellular epitope of the B-cell receptor (BCR) beta chain and its weak or absent expression in CLL may derive from the expression of a truncated form. This, together with the low expression of CD22, might explain the abnormal signal transduction of CLL cells similar to that of anergic B lymphocytes. Because no single marker is specific for CLL, a composite phenotype considering this set of 5 or 6 markers compounded into a scoring system helps to distinguish CLL from the other B-cell malignancies. Immunophenotypic analysis has also been shown to be useful for minimal residual disease detection and adds valuable prognostic information because the expression of certain markers, such as FMC7 or CD38, seems to be associated with a poor outcome. In addition, CLL cells express a variety of Bcl-2 family proteins with a profile that favors inhibition of apoptosis which, together with the interaction with microenvironmental (e.g. stromal) cells and the release of cytokines, explains the long life span and subsequent accumulation of CLL cells in various organs. Despite controversies relating to the expression of adhesion molecules (selectins and integrins) in CLL cells, it appears that some of these molecules do play a role in the pathogenesis, biology and clinical patterns of the disease. In conclusion, morphology and immunophenotype are the two essential investigations, which must be carried out in all cases of CLL. Both provide relevant information in terms of diagnosis, course of the disease, prognosis and pathogenesis.
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PMID:Morphological and immunophenotypic features of chronic lymphocytic leukemia. 1148 29

Chronic lymphocytic leukaemia is the commonest adult leukaemia, however the pathogenesis is largely unknown. Since the 1980s specific chromosomal abnormalities have been identified, of which the commonest are deletions of chromosomes 6q, 11q23, 13q14 and 17q13 and trisomy 12. The search for the responsible oncogenes at these sites has proved to be extremely frustrating. There are many oncogenes at 11q23 but the exact gene(s) responsible have yet to be identified. Germline abnormalities of the ATM gene occur in about 18% of patients compared to a normal population carriage of 0.5% but not all studies agree that ATM is the gene responsible. Unfortunately, despite the identification of various minimally deleted regions and the full sequencing of 13q14 no oncogenes have been identified. All original studies suggested the presence of a autosomally recessive tumour suppressor gene at this site but more recent studies suggest this may not be the case and the pathogenesis is more complex than first thought. Similarly, no genes have been identified at 6q or on chromosome 12. We know that the p53 tumour suppressor gene at 17p13 is an important prognostic indicator but it occurs in a minority of patients (about 15%), usually in patients with advanced disease, and therefore probably is not of aetiological importance.
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PMID:Molecular abnormalities in B-cell chronic lymphocytic leukaemia. 1155 53

Bladder cancers are classified as: transitional cell carcinoma (TCC), the most frequent in Europe/USA, squamous cell carcinoma (SCC), more frequent in the Middle East and in Africa, adenocarcinoma and small cell carcinoma, rare. TCC exhibit pseudo diploid karyotypes with only a few anomalies in early stages, evolving towards pseudo-tetraploides complexes karyotypes. Partial or complete monosomy 9 (-9) is an early event, found in half cases. Deletion (11p) or -11 is found in 20-50% of cases, more often in high grade and invasive tumours. Del(13q) is found in 25% of cases and correlated with high grade/stage; tumours with Rb alterations are invasives. Del(17p) is a late event, found in 40% of cases; P53 alterations are correlated with grade and stage, tumour progression, and a worse prognosis. Del(1p), i(5q), +7, and many other rearrangements - more often deletions than duplications - are frequently found. These losses of heterozygocity point to a multistep complex process involving tumor suppressor genes. In SCC, monosomy 9 is also an early event, even more frequent than in TCC; homozygous deletion of P16 is frequent. Trisomy 7 seems to be more frequent than in TCC. Chromosome 17 is often implicated, especially in high grades/stages; the profile of mutations of P53 is different from what is found in TCC. Allelic losses of 3p, 8p, 9p, 9q, 17p are frequent. The karyotype is more complex in advanced grades/stages, as in TCC.
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PMID:[From cytogenetics to cytogenomics of bladder cancers]. 1188 56

Ovarian neoplasms display a wide range of phenotypic differentiation patterns. In the recent past, molecular genetic aberrations have been increasingly identified in various types of ovarian tumors. Granulosa cell tumors most often contain numeric chromosomal aberrations (monosomy 22, trisomy 12 and 14). Numeric changes can also be found in benign and borderline epithelial neoplasms, however without demonstrating specific patterns. K-ras mutations are characteristic for mucinous ovarian tumors and for serous borderline (LMP) tumors. In serous LMP tumors they are associated with low level microsatellite instability. Complex chromosomal aberrations are not detected in benign and borderline tumors. Invasive ovarian carcinomas show complex genetic changes. Chromosomal gains at 3q26, 8q24 and 20q13 apparently represent early lesions, whereas loss of material of chromosomes 4, 13, 16, 18 and X is associated with tumor progression and poor prognosis. The main targets of chromosomal changes are regulatory genes of cell proliferation and apoptosis (e.g. p16, cyclin D1, Rb, p53, myc, bcl-2) and members of the signaling cascade of tyrosine kinase receptors (e.g. Her-2/neu, dab-2, K-ras, PI3-K, PTEN). The genetic alterations of ovarian neoplasms described so far apparently correlate with the different level of aggressiveness. However, they do not fully explain the spectrum of phenotypic variability of these tumors.
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PMID:[Phenotype--genotype--correlation in ovarian neoplasia]. 1189 92

The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is dependent on Helicobacter pylori infection. Bacterial colonisation of the gastric mucosa triggers lymphoid infiltration and the formation of acquired MALT. The bacterial infection induces and sustains an actively proliferating B-cell population through direct (autoantigen) and indirect (intratumoral T cells specific for H. pylori) immunological stimulation. Moreover, the bacterial infection provokes a neutrophilic response, which causes the release of oxygen free radicals. These reactive species may promote the acquisition of genetic abnormalities and malignant transformation of reactive B cells. A transformed clone carrying the translocation t(1;18)(q21;q21) forms a MALT lymphoma, the growth of which is independent of H. pylori and will not respond to bacterial eradication. Malignant clones without t(11;18)(q21;q21), but with other genetic abnormalities, such as trisomy 3 or microsatellite instability, depend critically on immune stimulation mediated by H. pylori for their clonal expansion. In the early stages, the tumour can be successfully treated by eradication of the bacterium, whereas at later stages the tumour may escape its growth dependency through acquisition of additional genetic abnormalities such as t(1;14)(p22;q32) and t(1;2)(p22,p12) involving the BCL-10 gene. Finally, further genetic abnormalities, such as inactivation of the tumour suppressor genes, p53 and p16, can lead to high-grade transformation. Detection of these abnormalities may help with the clinical management of patients with gastric MALT lymphoma.
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PMID:Gastric MALT lymphoma: from aetiology to treatment. 1190 29

This study evaluates the prognostic significance of genetic abnormalities (detected at or shortly after presentation), clinical stage, lymphocyte morphology, CD38 expression, and IGVH gene status in 205 patients with chronic lymphocytic leukemia (B-CLL). Deletion of chromosome 11q23, absence of a deletion of chromosome 13q14, atypical lymphocyte morphology, and more than 30% CD38 expression are significantly associated with the presence of unmutated IGVH genes. Advanced stage, male sex, atypical morphology, more than 30% CD38 expression, trisomy 12, deletion of chromosome 11q23, loss or mutation of the p53 gene, and unmutated IGVH genes are all poor prognostic factors in a univariate analysis. However, only 98% or more homology of IGVH genes to the germline sequence, loss or mutation of the p53 gene, and clinical stage retain prognostic significance in a multivariate analysis. The median survival of patients with mutated IGVH genes, unmutated IGVH genes, and loss or mutation of the p53 gene regardless of IGVH gene status is 310, 119, and 47 months, respectively. These data should facilitate the design of new trials for the management of patients presenting with advanced disease or poor prognosis early stage disease.
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PMID:Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. 1214 85

The cytogenetic abnormalities of granulosa cell tumors (GCT) of the ovary are only partially known. Up to now, mainly numerical chromosomal aberrations have been described. Therefore we performed a comprehensive study on paraffin-embedded material of 20 GCT (17 adult, 3 juvenile; patient age between 16 and 78 y) combining comparative genomic hybridization (CGH); fluorescence in situ hybridization (FISH) using DNA-specific probes for chromosome 12, 17, 22, and X; DNA cytometry; and immunohistochemistry (inhibin, p53, Ki67). By DNA cytometry, 16 of 20 tumors (80%) were diploid. However, 6 of 16 diploid tumors (37%) showed aberrations by FISH. FISH revealed monosomy 22 in 8/18 cases (40%); trisomy 12 in 5/20 (25%); monosomy X in 2/20 (10%); and loss of chromosome 17 in one case (5%). The main findings by CGH were gains of chromosomes 12 (6 cases, 33%) and 14 (6 cases, 33%) and losses of chromosomes 22 (7 cases, 35%) and X (1 case, 5%), mostly comprising whole chromosomes or chromosome arms. Inhibin and p53 were expressed in 100% and 95% of the tumors, respectively. The Ki67 index ranged from 0% to 61%. Neither immunohistochemistry, nor DNA cytometry and molecular genetic analysis, provided statistically significant prognostic information. In summary, our study reveals a distinctive pattern of cytogenetic alterations in GCT. Our observations confirm earlier reports that trisomy 12 and 14 are frequent aberrations; however, monosomy 22 seemingly is even more prevalent.
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PMID:Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors. 1221 13

ET is a chronic myeloproliferative disorder rarely evolving into AML, sometimes preceded by a myelodysplastic syndrome (MDS). Such transformations mostly occur in patients treated with radiophosphorous ((32)P) or alkylating agents, especially busulfan. Recently, concern has also arisen about the long-term safety of hydroxyurea (HU). Pipobroman (PI), a well tolerated and simple to use drug, constitutes a valid alternative to those cytoreductive treatments. The present study reports on 155 ET patients treated at our institution from 1985 to 1995, and monitored until December 2000. A good control of thrombocytosis was achieved with PI as the only treatment in 106 patients and with HU in 23 patients. Twenty-six patients received no treatment. After a median follow-up of 104 months, seven patients (four treated with HU, and three with PI) developed AML whereas one patient treated with PI developed MDS. A significant difference in progression-free survival was observed between HU- and PI-treated patients (P = 0.004). A short-arm deletion of chromosome 17 was most frequently detected in HU-treated patients, while a long-arm trisomy of chromosome 1 and a monosomy 7q were seen in PI-treated patients. No TP53 mutation was discovered in the six patients studied (two HU-treated and four PI-treated). We conclude that these cytogenetic abnormalities are not linked to the natural history of the disease, but rather that they might be induced by the cytoreductive treatment.
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PMID:Acute myeloid leukemia (AML) having evolved from essential thrombocythemia (ET): distinctive chromosome abnormalities in patients treated with pipobroman or hydroxyurea. 1235 60


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