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)

Many human cancers are characterized by mutations of p53, a nuclear phosphoprotein which controls elements of the cell cycle. Turnover of p53 in normal cells is rapid, and the minute quantities of protein that are usually present are not detected by immunocytochemical methods. Mutations of the p53 gene in tumour cells are associated with a slower turnover and subsequent accumulation of the protein in both nucleus and cytoplasm. Genetic abnormalities of the short arm of chromosome 17, which is the site of the p53 gene locus, are a feature of astrocytic tumours. Using a panel of five antibodies to p53 and a standard immunocytochemical method, we found detectable quantities of p53 in the cells of 3/16 diffuse astrocytomas, 8/14 anaplastic astrocytomas, and 24/34 glioblastoma multiforme. Progression of one patient's tumour from a diffuse to an anaplastic astrocytoma was characterized by the accumulation of p53. The more malignant histological features of anaplastic astrocytoma and glioblastoma multiforme appear to be reflected by a greater incidence of p53 accumulation.
 ...
PMID:Expression of the p53 protein in a spectrum of astrocytic tumours. 133 44

The human brain tumor, astrocytoma, typically progresses through three histopathologically defined stages with the passage of time: one premalignant stage, low-grade astrocytoma; and two malignant stages, anaplastic astrocytoma and glioblastoma multiforme. We correlated the results of a sequence analysis of the tumor suppressor gene, p53, and a restriction fragment length polymorphism analysis of chromosomes 17 and 10 in 45 patients with cerebral astrocytomas at different stages. To detect p53 mutations in tumor DNA, we analyzed polymerase chain reaction products corresponding to every p53-coding exon for single-strand conformation polymorphisms and confirmed the mutations by sequencing. Loss of heterozygosity (LOH) was determined by Southern transfer analysis of somatic and tumor DNA from these same patients using polymorphic markers for various loci on chromosomes 10 and 17. p53 mutations were found in 7 of 25 glioblastomas (28%), in 5 of 14 anaplastic astrocytomas (36%) but in 0 of 6 low-grade astrocytomas. p53 mutations were found in 62% of patients with LOH on chromosome 17p. These results indicated that p53 inactivation is a common genetic event in astrocytoma progression that may signal the transition from benign to malignant tumor stages. LOH on chromosome 10 was found in 61% of glioblastomas, in 23% of anaplastic astrocytomas, but in 0% of low-grade astrocytomas. LOH on chromosome 10 and p53 mutation were found together only in patients with glioblastoma multiforme (22%), suggesting that these genetic changes may accumulate during astrocytoma progression.
 ...
PMID:p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression. 134 55

Astrocytomas, including the most malignant form, glioblastoma multiforme, are the most frequent and deadly primary tumors of the human nervous system. Recent molecular genetic analyses of astrocytomas have demonstrated frequent chromosome 17 deletions involving the telomeric region of the short arm (17p12-pter). This region contains a candidate tumor suppressor gene, TP53, which has recently been implicated in the etiology of a broad array of human cancers. To study the possible role of TP53 in astrocytoma development, 24 randomly chosen human astrocytic tumors were examined for genomic TP53 sequence aberrations using primer-directed DNA amplification in conjunction with direct sequencing. Five of the 11 grade III astrocytomas (glioblastoma multiforme), but only one of seven grade II astrocytomas (anaplastic astrocytoma) and none of either the grade I astrocytomas or oligodendrogliomas demonstrated distinct point mutations involving the TP53 gene. These data suggest that TP53 mutations may play a role in astrocytoma development and are predominantly associated with higher grade tumors.
 ...
PMID:TP53 gene mutations and 17p deletions in human astrocytomas. 168 25

Single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP analysis) was used for detection of mutations of the p53 gene in surgical specimens of human brain tumors. Six of 45 brain tumors showed mobility shifts in the analyses. These six tumors also showed loss of a normal allele. The samples were examined further by direct sequencing. Results showed that four of them had single-base substitutions and the other two had deletions of one and eight base pairs. Five of the six mutations detected were clustered in highly conserved regions of the p53 gene. The frequency of p53 gene mutations in primary brain tumors examined was 9.8%. We also found two new polymorphic markers in the p53 gene, one in intron 7 and the other in an Alu repeat in exon 11. Both markers could be detected by SSCP analysis. Using these two markers, we found two cases of loss of heterozygosity in other brain tumor specimens. Results suggested that aberrations of the p53 gene were not correlated with the malignancy of some types of brain tumors such as anaplastic astrocytoma and glioblastoma, contrary to previous observations on colorectal cancers.
 ...
PMID:Detection of p53 gene mutations in human brain tumors by single-strand conformation polymorphism analysis of polymerase chain reaction products. 188 8

Mutations of the p53 tumor-suppressor gene, as determined by the immunohistochemistry of archival formalin-fixed specimens, have been correlated with the prognosis for patients with many different types of malignancy. Similar correlations have been shown in series including patients with all grades of astrocytoma. We hypothesized that this might be a clinically useful prognostic indicator for patients with a defined grade of astrocytoma, anaplastic astrocytoma. This series comprised 54 consecutive patients with biopsy-proven anaplastic astrocytoma treated at one institution. When the CM-1 antiserum was used for testing, 33 (61%) of the 54 biopsies exhibited positive nuclear staining for p53, indicating an abnormal accumulation of the protein. This staining was graded according to the number of positive cells per high-power field. Positive immunohistochemical staining for p53 in the tumor cell nuclei did not correlate with the patient's outcome. Significant correlates of improved patient survival were the presentation with epilepsy in the absence of a neurological deficit (P = 0.005) and the surgeon's performance of a macroscopically complete surgical resection of the tumor (P = 0.01).
 ...
PMID:Aberrant p53 expression does not correlate with the prognosis in anaplastic astrocytoma. 747 76

Among tumours of the nervous system, mutations of the p53 tumour suppressor gene are largely restricted to neoplasms of astrocytic origin. These are the most common human brain tumours and span a wide range of biologic behavior, from the slowly growing low-grade astrocytoma (WHO Grade II) to anaplastic astrocytoma (WHO Grade III) and, ultimately, the glioblastoma multiforme (WHO Grade IV). In low grade astrocytomas, p53 mutations with or without loss of heterozygosity on chromosome 17p are the principle detectable change. Anaplastic astrocytomas contain p53 mutations in approximately one third of cases and further display loss of heterozygosity on chromosome 19q and homozygous loss of 9p21, tentatively identified as multiple tumour suppressor 1 (MTS-1). In addition to these genetic alterations, glioblastomas show loss of chromosome 10 and amplification of the EGF receptor gene at an incidence of > 60% and > 40%, respectively. The type and distribution of p53 mutations are not suggestive of specific environmental carcinogens operative in their etiology.
 ...
PMID:Genetic alterations associated with glioma progression. 753 15

The treatment and prognosis of patients with cerebral astrocytic tumours are currently guided by histopathological classification. This study evaluates immunohistochemistry using Ki-67, an antibody to a nuclear protein expressed in proliferating cells, and DO-7, an antibody to the product of the tumour suppressor gene p53, as prognostic indicators for these tumours. Immunohistochemistry with Ki-67 has been correlated with the behaviour of many different tumours, but its value as a prognostic indicator in astrocytic tumours is diminished by the conflicting results of previous studies. Immunohistochemistry with antibodies to the p53 protein has been used as a prognostic indicator in melanomas and some carcinomas, but the relation between prognosis and accumulation of this protein in astrocytic tumours has not been clarified. We have tested the hypothesis that survival is correlated with Ki-67 immunolabelling indices (LIs) and patterns of p53 immunolabelling in the cerebral astrocytic tumours of a large cohort of patients (n = 123) for whom clinical indices were well documented. Astrocytic tumours were divided into three histological types: fibrillary astrocytoma (n = 24), anaplastic astrocytoma (n = 31), and glioblastoma (n = 68). Histological type and patient age were independent predictors of survival. Median Ki-67 LIs differed significantly (P < 0.0001) between the types of astrocytic tumour, and tumours with a Ki-67 LI < 2% had a significantly (P < 0.0001) better prognosis. Ki-67 LI as a continuous variable carried a significant (P = 0.0043) unadjusted hazard to survival which was lost when adjusted for other variables, notably histological type. By contrast, no relation was found between survival and three categories of p53 labeling (p53-negative, p53 LI < 40%, and p53 LI > 60%). The results indicate that, whereas Ki-67 immunohistochemistry predicts survival in patients with astrocytic tumours, conventional histological appraisal remains the best guide to prognosis, and immunohistochemistry for p53 has no value in the assessment of these tumours.
 ...
PMID:Prognostic indicators in a range of astrocytic tumours: an immunohistochemical study with Ki-67 and p53 antibodies. 756 22

We investigated the frequency of p53 mutations in 47 pediatric brain tumors of various histologic subtypes that were collected over a period of 5 years. The specimens included 15 primitive neuroectodermal tumors (PNETs), 17 low grade astrocytomas, one anaplastic astrocytoma, three glioblastomas (GBMs), one mixed glial tumor, eight ependymomas, one choroid plexus carcinoma, and one gangliocytoma/ganglioneuroma. Mutations were identified by single strand conformation polymorphism analysis of exons 4-8 and verified by sequencing. Mutations were present in 2 of 3 cases of GBM, but not in 17 low grade astrocytomas (P = 0.02, Fisher's exact test). One GBM demonstrated a germline GGC to AGC transition (gly to ser) at codon 245 with loss of the wild-type allele. A second GBM contained a CGG to TGG transition (arg to trp) at codon 248, also with loss of the wild-type allele, but normal tissue was not available for comparison. In addition, one of 15 PNETs retained heterozygosity but demonstrated a somatic CGT to TGT transition (arg to cys) at codon 273. p53 mutations were absent in other histologic subtypes and in two cases with multiple primary cancers. These data are consistent with earlier findings that p53 mutations are rare in PNETs, which are primarily pediatric tumors. In contrast to adult gliomas, p53 mutations in pediatric gliomas appear restricted to the GBMs. The lack of p53 mutations in pediatric low grade astrocytomas suggests not only histological differences, but also a different molecular pathogenesis in adult and pediatric patients.
 ...
PMID:p53 gene mutations in pediatric brain tumors. 756 4

Diffusely infiltrating low-grade astrocytomas (WHO grade II) have an intrinsic tendency for progression to anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV). This change is due to the sequential acquisition of genetic alterations, several of which have recently been identified. In low-grade astrocytomas, p53 mutations with or without loss of heterozygosity on chromosome 17p are the principal detectable change. Anaplastic astrocytomas contain p53 mutations at an overall incidence of 34% and, in addition, loss of heterozygosity on chromosome 19q and frequent homozygous deletion of the p16 tumor suppressor (MTS-1) gene. The most malignant astrocytic neoplasms, the glioblastoma, further shows loss of chromosome 10 and amplification of the epidermal growth factor receptor (EGF-R) gene at overall incidences of 66% and 34%, respectively. The type and distribution of p53 mutations in astrocytic brain tumours are not suggestive of specific environmental carcinogens operative in their aetiology. Analysis of 91 families with p53 germline mutations reported to date show that tumours of the nervous system account to 12% of all neoplasms. Of a total of 57 brain tumours reported, 30 were classified histologically and of these, 73% were of astrocytic origin. The observation that somatic p53 mutations in sporadic brain tumours are largely restricted to those of astrocytic origin and that astrocytomas also prevail among CNS neoplasms associated with p53 germline mutation strongly suggests, that p53 mutations are capable of initiating neoplastic transformation in astrocytes of the human nervous system.
 ...
PMID:Genetic alterations associated with the evolution and progression of astrocytic brain tumours. 758 39

This report describes clinical, neuropathological and molecular genetic findings in a Swiss family with four brain tumours in only two generations. The neoplasms observed covered a wide range of biologic behaviour, from a slowly growing lesion already apparent at birth, to anaplastic astrocytoma in a young adult and glioblastomas at the age of less than 10 years. The only non-neural neoplasms in this family were a case of leukemia and an adrenocortical carcinoma. A germline deletion of codon 236 of the p53 tumour suppressor gene was identified as an underlying cause and detected in all affected family members. This mutation has not previously been reported as germline transmission or in sporadic tumours. The unusual accumulation of CNS tumours may be due to a certain organ-specific effect of this particular p53 mutation or it may reflect the specific genetic back-ground of this family.
 ...
PMID:Familial brain tumour syndrome associated with a p53 germline deletion of codon 236. 776 87


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