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

Gastric carcinogenesis is attributable to interacting environmental and genetic factors, through a sequence of events including intestinal metaplasia. Using a fluorescence in situ hybridization technique, we investigated the occurrence of aneuploidies of chromosomes 3, 7, 8, 9, and 17, TP53 gene deletion, and expression of p53 in 21 intestinal metaplasia (IM) samples from cancer-free patients and in 20 gastric adenocarcinoma samples. Aneuploidies were found in 71% (15/21) of the IM samples. Trisomy of chromosomes 7 and 9 occurred mainly in complete-type IM; in the incomplete type, trisomy of chromosomes 7 and 8 were more commonly found. The TP53 gene deletion was observed in 60% (3/5) of the IM cases, and immunohistochemistry revealed p53 overexpression in 12% (2/17) of the analyzed IM cases. All gastric adenocarcinoma cases presented higher frequencies of trisomy or tetrasomy of chromosomes 3, 7, 8, 9, and 17. The TP53 deletion was found in all three of the gastric adenocarcinoma analyzed for it, and immunohistochemistry detected overexpression of protein p53 in 80% (12/15) of the analyzed cases. Our study revealed for the first time the presence of aneuploidies of chromosomes 7, 8, 9, and 17 and of TP53 gene deletion and overexpression in IM samples from cancer-free patients. These results suggest that IM and gastric adenocarcinoma may share the same genetic alterations.
 ...
PMID:Aneuploidies, deletion, and overexpression of TP53 gene in intestinal metaplasia of patients without gastric cancer. 1535 Mar 2

Female rats of the inbred strain BDII are genetically predisposed to endometrial estrogen-dependent adenocarcinomas (EAC). More than 90% of them spontaneously develop this tumor type before the age of 24 months. In order to dissect out the genetic components behind these tumors we have made crosses between BDII females and rats from 2 other strains that are nonsusceptible to EAC. It was found that EAC tumors developed in a subset of intercross and backcross animals from both interstrain crosses. The chromosomal changes in the developing tumors were studied using cytogenetic and molecular cytogenetic methods. From these studies, we conclude that certain chromosome regions were recurrently engaged in chromosomal changes such as increases in copy number (e.g., trisomy, amplification) or decreases (e.g., deletion). Based on the analysis of 56 tumors, 8 regions were found to be particularly often involved: RNO4prx, gain=34 (61%) (amplification 12 cases); RNO5mid, loss=15 (27%); RNO6prx, gain=25 (45%) (amplification 8 cases); RNO10 loss, prx-mid/gain dst=25 (45%) (amplification 1 case); RNO12q, gain=23 (41%); RNO15p loss/RNO15q gain=29 (52%) (amplification 1 case) [RNO, rat chromosome; prx, proximal; mid, middle; dst, distal; p, short arm; q, long arm]. We begun to analyze these regions in detail using various molecular methods and within them there are certain possible target genes, such as MET (RNO4q21), CDKN2A/2B (RNO5q32), MYCN (RNO6q15 approximately q16), and TP53 (RNO10q24 approximately q25), but it is clear that several other genes, still unidentified, must also be involved.
 ...
PMID:Cytogenetic aberrations in spontaneous endometrial adenocarcinomas in the BDII rat model as revealed by chromosome banding and comparative genome hybridization. 1589 83

The presence of chromosome abnormalities promotes tumor progression in B-chronic lymphocytic leukemia (CLL). However, the molecular pathways that are relevant to tumor progression remain unclear. In this study, we screened for common chromosome abnormalities [13q14 del, 11q22.3 (ATM) del, 17p13 (p53) del and trisomy 12] by fluorescent in situ hybridization in 40 B-CLL patients. Each of the four chromosome abnormality groups was compared to several clinical factors related to lymphocyte behaviour in CLL. The 11q22.3 (ATM) deletion group was significantly associated with the presence of bulky abdominal/mediastinal lymphadenopathy (P = 0.014). We hypothesized that this phenotype would be associated with an altered transcription pattern of genes. Class comparison analysis by significance analysis of microarrays on a subset of CLL samples (n = 14) indicated that a number of cell surface receptor and adhesion related genes were under-expressed in the 11q22.3 deletion group (CD44, CD11a, PTPRC, CD79a, chemokine ligand 17 and chemokine receptor type 6). The presence of additional prognostic factors, such as CD38 and immunoglobulin heavy chain variable region mutational status, may also influence the transcriptional pathways between the two groups. Therefore, we employed a novel analysis technique for the correlation of log(2) gene expression ratios with the percentage of each tumor that carried the 11q22.3 deletion. Using Spearman's correlation, ZAP-70, chemokine ligand 17, BSAP (PAX5), CD7, LAG3 and PTPR6 were significantly correlated with the percentage of cells with the 11q22.3 deletion. However, the down-regulation of cell surface receptors and adhesion molecules observed by class comparison could not be confirmed to be specific for the 11q22.3 deletion by this method.
 ...
PMID:11q22.3 deletion in B-chronic lymphocytic leukemia is specifically associated with bulky lymphadenopathy and ZAP-70 expression but not reduced expression of adhesion/cell surface receptor molecules. 1632 52

The t(14;18)(q32;q21) involving the MALT1/MLT and IGH genes has been identified recently as a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. The frequency of secondary chromosomal aberrations in MALT lymphomas harboring the t(14;18) is largely unknown. We therefore analyzed six t(14;18)-positive MALT lymphomas (five parotid, one conjunctiva) by interphase fluorescence in situ hybridization for aneuploidies of chromosomes 3, 7, 12, 18, and X, gains or disruption of the CMYC/8q24 and BCL6/3q27 genes, as well as deletions of the retinoblastoma and TP53 tumor suppressor genes. Except for one MALT lymphoma of the parotid with trisomy 3, neither aneuploidies nor deletions were detected in any of our cases.
 ...
PMID:Frequency of chromosomal aneuploidies and deletions of the RB and TP53 genes in MALT lymphomas harboring the t(14;18)(q32;q21). 1636 68

A panel of fluorescence in situ hybridisation (FISH) probes was used on 894 cases to target chromosome 11q, 13q, 17p deletions (del), trisomy 12 (+12) in all and 6q deletion in 59. Chronic lymphocytic leukaemia (CLL) immunophenotype (CD5 and CD19 with CD23) was found in 509 cases (average age 67.7 years, 319 males and 190 females). Among the 509 CLL cases 349 (68.6%) had FISH (4-probe panel) abnormalities: 160 del 13q [45.8% (122-del 13q, 18-biallelic del 13q, 20-monoallelic/biallelic del 13q)], 71 tri 12 (20.3%), 17 del ATM (5%), 12 del p53 (3.4%) and 89 > or = 2 FISH abnormalities (25.5%). Of 151/509 cases karyotyped, 108 were normal and 43 (43/151 = 28.5%) abnormal. Del 6q was found in 1/59 (1.6%) FISH cases and in 6/151 (4%) karyotypes. In 14 CD23 negative cases IGH/BCL1 FISH detected t(11;14) and was confirmed to be mantle cell lymphoma. Multiple probes/panels that included IGH probe were ordered for 57 CLL cases, 11 had an IGH rearrangement with an unidentified partner. This study favours the inclusion of del 6q and IGH probes in the CLL panel. The FISH panel could also serve to monitor 13q deletion for secondary changes with adverse prognosis. Understanding prognosis in specific types of 13q deletion would enhance outcome prediction.
 ...
PMID:Chronic lymphocytic leukaemia profiled for prognosis using a fluorescence in situ hybridisation panel. 1648 71

The most frequent genetic aberrations in multiple myeloma (MM) are 13q deletions and translocations involving the immunoglobulin heavy chain gene (IGH). There have been no reports on the cytogenetic abnormalities found in Korean patients with MM. We investigated the actual prevalence and prognostic value of cytogenetic changes using fluorescence in situ hybridization (FISH). FISH studies with 12 different specific probes for the regions containing the genes or chromosome regions (13q, 1q, IGH, p53, MLL, p16, CEP 7, CEP 11, and CEP 12) were performed in 128 patients. The most frequent change found was 13q deletion (48%), followed by trisomy 1q (45%), IGH translocation (37%), and trisomy 11 (26%). Among the three different probes used to detect 13q deletion, D13S25 (48/58) was the most sensitive probe compared to RB (43/58) and D13S319 (39/58). Among the patients showing one or more changes by FISH, 75% (82/110) had a 13q deletion, a trisomy 1q, or an IGH translocation. Azotemia, anemia, thrombocytopenia, intramedullary plasmacytosis, and stage were significantly associated with the 13q deletion; serum beta(2)-microglobulin, thrombocytopenia, and intramedullary plasmacytosis were also related to trisomy 1q. The pattern of molecular cytogenetic changes in Korean patients with MM is somewhat different from what has been observed in reported Caucasian populations: 37 versus 50-70% with regard to the IGH translocation. The prevalence of the 13q deletion was similar in Korean and Caucasian populations, 48 versus 30-50%. We suggest that the detection of at least these three genetic changes, 13q- trisomy 1q, and an IGH rearrangement, would be helpful for follow-up of Korean patients with MM.
 ...
PMID:Identification of 13q deletion, trisomy 1q, and IgH rearrangement as the most frequent chromosomal changes found in Korean patients with multiple myeloma. 1684 2

Glioblastoma is the most common primary tumor of the central nervous system, but the underlying genetic changes that give rise to these tumors are still poorly understood. We report a primary glioblastoma with an unusual age of presentation. The patient was a 22-year-old man with a survival of 16 months. Morphological findings showed an increase of cellularity with positive GFAP and EGFR expression, increase of proliferate index, vascular hyperplasia with glomeruloid structures and necrosis. Molecular analysis showed EGFR amplification. No mutations of the TP53 or amplification of MDM2 and CDK4 were detected. Neither homozygous deletion of the 9p21 locus genes nor aberrant methylation were found. The cytogenetic study showed a clonal karyotype. The metaphases presented, among other anomalies, a small ring chromosome and double-minutes chromosomes. Using FISH and CGH techniques, it was found that the ring chromosome was a partial trisomy of chromosome 7, and the region implicated corresponded to 7p13-q21. Partial trisomies in glioblastoma could play an important role in defining those regions where genes implicated in this tumor process may be found. We studied the possible correlation of these findings with the tumoral phenotype.
 ...
PMID:Primary glioblastoma with EGFR amplification and a ring chromosome 7 in a young patient. 1686 1

By multiparameter flow cytometry, the T-cell-associated markers CD4 and CD7 were aberrantly coexpressed on a case of B-cell chronic lymphocytic leukemia (CLL). The CLL had an immunophenotype: CD19+, CD20+, CD79b+, CD5+, CD23+, FMC7+, kappa+, CD4+, and CD7+. Molecular analysis confirmed clonal rearrangement of the immunoglobin heavy chain genes and a germline configuration of the T-cell receptor genes. Fluorescence in situ hybridization showed trisomy 12 anomaly. There was no evidence of deletion 17p (p53), 11q23 (ATM), or 13q14 or translocation t(11:14). The patent was clinically stable without treatment. Although the pathogenesis of such aberrant immunophenotype remains to be determined, the current case illustrates the phenotypic heterogeneity of CLL, and emphasizes the importance of a comprehensive diagnostic approach including clinical, morphologic, immunophenotypic, and molecular cytogenetic studies.
 ...
PMID:Aberrant expression of T-cell-associated markers CD4 and CD7 on B-cell chronic lymphocytic leukemia. 1701 87

B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in the elderly population. Under conventional cytogenetic (CC) analysis, approximately 50% of CLL cases show clonal aberrations. Using fluorescent in situ hybridization (FISH), the percentage of patients with abnormalities rises to almost 80%, the most frequent being 13q14, ATM, and TP53 deletions and trisomy 12. The aim of this study was to establish the incidence of genetic changes in B-CLL patients using CC and FISH and to evaluate the prognostic implications. Of the 65 patients analyzed, genetic aberrations were found in 36.7% with CC and in 68.4% with FISH. The frequencies of abnormalities were as follows: 13q deletion, 42.1%; trisomy 12, 19.2%; ATM deletion, 17.5%; and TP53 deletion, 8.7%. Significant differences were observed when the overall survival was correlated with Rai stage (P = 0.000). FISH abnormalities were correlated with age, sex, morphology, white blood cell count, CD38 expression, Rai stage, disease status, and survival. Significant differences were obtained with age (P = 0.05) and disease status (P = 0.01). Deletion of 13q was the most frequent abnormality (36.6%) among old patients (> or =60); trisomy 12 was the most frequent (31.3%) in younger patients (<60). Half of the patients with stable disease showed 13q deletion, and the most frequent abnormality in patients with progressive disease was ATM deletion (22.2%).
 ...
PMID:Genetic abnormalities and clinical outcome in chronic lymphocytic leukemia. 1707 92

We explored the relationship between the cytogenetic/biologic characteristics of B-chronic lymphocytic leukemia (B-CLL) cells and their tendency to undergo spontaneous or fludarabine-induced apoptosis in vitro. B cells from 36 B-CLL patients were incubated with or without fludarabine for 48 h. Apoptosis was determined by two assays: annexin V staining and DNA staining. Fluorescence in situ hybridization was used for detection of trisomy 12, 11q deletion, and 17p deletion. Bcl-2 and CD38 expressions were determined by flow cytometry. Five patients had 17p deletion, 6 had trisomy 12, and another 6 had 11q deletion. B-CLL cells with 17p deletion had significant resistance to apoptosis induced by fludarabine and a slight spontaneous resistance to apoptosis. Bcl-2 and CD38 were not associated with in vitro spontaneous and fludarabine-induced apoptosis. In conclusion, 17p deletion, which causes loss of p53 gene, is associated with resistance to fludarabine-induced apoptosis in vitro. New treatment modalities should be tried in B-CLL patients with 17p deletion.
 ...
PMID:17p Deletion is associated with resistance of B-cell chronic lymphocytic leukemia cells to in vitro fludarabine-induced apoptosis. 1732 77


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>