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)

Non-familial human adrenocortical adenomas and carcinomas were screened for mutations in exons 5-8 of the p53 tumor suppressor gene by single-strand-conformation-polymorphism (SSCP) analysis, followed by direct sequencing of PCR-amplified DNA. Point mutations in codons 12, 13 and 61 in H-ras, K-ras and N-ras proto-oncogenes were similarly assessed by direct DNA sequencing. Three out of 15 primary adrenocortical carcinomas (20%) contained a mis-sense point mutation in the conserved regions (exons 5 and 8) of the p53 gene. Mutations were located in codon 157 (GTC-->TTC; Val-->Phe), codon 163 (TAC-->AAC; Tyr-->Asn), and codon 273 (CGT-->TGT; Arg-->Cys). The mutation in codon 157 was detected in the primary tumor as well as in brain and lymph-node metastases. Among 18 adrenocortical adenomas, there was only a single non-miscoding mutation in codon 295 (CCT-->CCC; Pro-->Pro). These data suggest that mutational inactivation of the p53 gene occurs in a minority (20%) of sporadic adrenocortical carcinomas and that these mutations constitute a late event in the multi-step process of malignant transformation. No ras mutations were detected in any of these tumors, suggesting that these genes are not involved in the development of tumors originating from the adrenal cortex.
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PMID:p53 mutations in sporadic adrenocortical tumors. 850 16

It has recently been shown that point mutations of the TSH-R or G(alpha)s genes are associated with autonomous hyperfunctioning thyroid adenomas and differentiated carcinomas. We therefore screened for mutations in the TSH-R, G(alpha)s, ras and p53 genes in nine rat transplantable thyroid carcinoma lines derived from tumors induced by DHPN as a chemical carcinogen. Mutations were identified using single-strand conformation polymorphism and DNA sequencing analysis. Point mutations in G(alpha)s codon 201 (CGC-->CAC) were detected in three lines (33%), resulting in a heterozygous alteration (Arg-->His) in the expressed G(alpha)s protein. The mean intracellular cAMP level (2.30 +/- 0.27 nmol/mg) of the three mutated cell lines was significantly increased as compared with that of the lines (1.54 +/- 0.32 nmol/mg) without the G(alpha)s mutation (P < 0.01, by paired t-test). Also, these three cell lines had an activating mutation in Ki-ras codon 12 (GGT-->GAT). One TSH-R gene mutation was found with a base substitution in codon 636 (TGC-->TGT) but no amino acid change. No p53 gene (exons 5-8) mutations were detected in any of the cell lines analyzed. The results suggest that mutational activation of the G(alpha)s gene may play a tumorigenic role through constitutive activation of the cAMP pathway and that G-->A point mutations in the G(alpha)s and ras genes in thyroid carcinomas directly reflect interaction of the chemical carcinogen with guanine residues in DNA.
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PMID:Genetic alterations in N-bis(2-hydroxypropyl)nitrosamine-induced rat transplantable thyroid carcinoma lines: analysis of the TSH-R, G(alpha)s, ras and p53 genes. 905 17

The clinical and pathologic features of a rare case of follicular carcinoma with small foci of poorly differentiated and anaplastic carcinoma are presented. Eight years after the removal of the primary neoplasm, the patient developed pulmonary and brain metastases that were predominantly composed of the poorly differentiated and anaplastic components. A comparative immunohistochemical and molecular analysis of p53 status in the follicular, poorly differentiated and anaplastic components of the tumor was performed. p53 immunostaining was restricted to the poorly differentiated and anaplastic areas. Single strand conformation polymorphism analysis (SSCP-PCR) from DNA obtained by microdissection demonstrated the presence of a mutation (TAT-->TGT; Tyr-->Cys) in codon 220, exon six of the p53 gene in the anaplastic component, that was absent in the well-differentiated follicular areas. The results of that study in this rare tumor support that p53 has a tumor progression role in thyroid tumorigenesis.
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PMID:p53 in a thyroid follicular carcinoma with foci of poorly differentiated and anaplastic carcinoma. 918 95

Dietary zinc deficiency in rats induces hyperplasia in the esophagus and increases N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence. Previous work showed a direct relationship between epithelial cell proliferation and esophageal tumor incidence in rats given multiple doses of NMBA. We investigated the effects of single low doses of NMBA in zinc-deficient rats since a single dose of 5.0 mg/kg was reported to be non-carcinogenic in rats. Zinc-sufficient and deficient rats received a single i.g. dose of NMBA at 0.5 or 2.0 mg/kg. At week 14, tumor incidence was 50% with 0.8 +/- 1.0 tumors/rat, and 80% with 2.2 +/- 1.9 tumors/rat, in deficient groups, D(0.5) and D(2.0), that received the lower and higher dose, respectively. In addition, two small papillomas were found in one out of eight untreated zinc-deficient rats. None of the NMBA-treated or untreated zinc-sufficient rats had any tumors. Esophageal cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry, showed that, irrespective of NMBA treatment, deficient esophagi had significant increases in the number of labeled cells, the total number of cells, and the labeling index, as compared with zinc-sufficient ones. Mutations in Ha-ras and p53 genes in esophageal tumors were detected by single strand conformation polymorphism (SSCP) analysis. DNA sequencing of variant conformers revealed a point mutation (GGA-->GAA, codon 12) in Ha-ras in 4/5 (80%) and 5/8 (63%) tumors, from D(0.5) and D(2.0) rats, respectively. Three out of eight tumors from D(2.0) rats exhibited SSCP mobility shifts within p53 exons 5 and 7: two tumors (2/8, 25%) had missense mutations and the third, a silent mutation. Of the two tumors with p53 mutations, one had a double mutation (transition at codon 164, TCA-->TTA; transversion at codon 241, AGT-->TGT), and the other tumor, a transition at codon 172 (AGA-->GGA), with amino acid changes in all cases. In parallel with PCNA expression, elevated p53 expression was associated with hyperplastic and dysplastic regions, as well as with tumors, in deficient esophagi. In short, these data indicate that dietary zinc deficiency, with its associated sustained increased cell proliferation in the esophagus, can drive an otherwise non-tumorigenic dose of NMBA into a highly tumorigenic one.
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PMID:Induction of esophageal tumors in zinc-deficient rats by single low doses of N-nitrosomethylbenzylamine (NMBA): analysis of cell proliferation, and mutations in H-ras and p53 genes. 927 19

Direct pulmonary instillation of 1,6-dinitropyrene (DNP) into male Fischer 344 rats results in a dose-dependent induction of lung tumors and 6-thioguanine-resistant (TGr) T-lymphocytes. The treatment also results in DNP binding to dG in the lung and in T-lymphocytes. In the present study, we have examined the types of mutations associated with these responses to DNP. Sequencing of DNA amplification products from 20 DNP-induced lung tumors identified 5 mutations in K-ras codon 12, 4 GGT-->TGT transversions and one GGT-->GAT transition. No mutations were found in K-ras codons 13 or 61. Single-strand conformation polymorphism analysis of p53 exons 5-8 revealed mobility shifts indicative of mutation in 9 of the 20 tumor samples. Eight of the mutations were substitutions at G:C base pairs, and one was a deletion of a single G:C base pair. DNA from 161 TGr lymphocyte colonies cultured from DNP-treated rats was examined for point mutations by amplification of hprt exons 2, 3, and 8, and screening the products for mutant: wild-type heteroduplex formation by denaturing gradient-gel electrophoresis. Only three mutations were found, a G-->T transversion in exon 3, a G-->A transition in exon 8, and a complex mutation consisting of a tandem G-->T transversion and a one base deletion in exon 3. The mutations identified in the DNP-induced lung tumors and TGr T-lymphocytes are consistent with the formation of dG-DNA adducts by DNP. The extremely low recovery of point mutations from TGr lymphocytes suggests that DNP induces a substantial number of mutations by other mechanisms.
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PMID:Analysis of mutations in the K-ras and p53 genes of lung tumors and in the hprt gene of 6-thioguanine-resistant T-lymphocytes from rats treated with 1,6-dinitropyrene. 933 Jun 23

The p21 protein inhibits the activity of cyclin-Cdk complexes and suppresses cell cycle progression. Wild type p53 can induce p21, but mutated p53 cannot. Previous studies have demonstrated that mutation of p53 is absent in neuroblastoma (NB). These reports prompted us to examine whether p53 induced p21 in NB. We examined the expression of p21 and p53 mRNA in eight NB, two Ewing's sarcoma (ES) and two primitive neuroectodermal tumor (PNET) cell lines by Northern blot analysis, and sequenced p53 cDNA of these cells. Although p53 mRNA was detected in all analyzed cell lines by Northern blot analysis, p21 mRNA was detected in six NB but not in two NB, two ES and two PNET cell lines. We detected the point mutation of p53 at codon 273 (CGT to TGT) in one NB and two ES cell lines. The non-transforming substitution at codon 72 (CCC to CGC) was detected in all analyzed cell lines. One PNET cell line had a large deletion of p53 cDNA. These results showed that p21 mRNA was usually expressed in NB but not in ES and PNET. This may suggest that the down stream of the p53 signal transduction pathway in NB is different from that of the closely related tumors of ES and PNET.
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PMID:p21 (WAF1/Cip1/Sdi1/Pic1) mRNA is expressed in neuroblastoma cell lines but not in Ewing's sarcoma and primitive neuroectodermal tumor cell lines. 936 58

A 60-year-old woman was admitted in June 1993, because of anemia and purpura and given a diagnosis of acute myelogenous leukemia with trilineage dysplasia. She entered partial remission (PR) after three courses of low-dose Ara-C and G-CSF, but never reached complete remission (CR) in spite of additional chemotherapy. In October 1994, the number of leukocytes, myeloblasts, and erythroblasts in the patient's peripheral blood increased, and her clinical condition deteriorated. The disease was resistant to other therapy. The patient had pneumonia and died of septic shock in December 1994. A chromosomal analysis performed on admission showed 46,XX,t(3;5) (q21;q31) [9/9]. As an additional chromosomal abnormality, deletion of the X chromosome was observed in January, 1994. Analysis of the p53 gene by the polymerase chain reaction-single strand conformation polymorphism method showed one base transposition, from TAT to TGT (Tyr to Cys), at codon 220 of exon 6. Karyotype evolution and p53 gene mutation were observed during the disease course and may have been related to progression of the disease.
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PMID:[t(3;5) (q21;q31) chromosomal abnormality in a patient with acute myelogenous leukemia with trilineage myelodysplasia]. 979 99

The histogenesis of carcinosarcoma of the breast is controversial. In the current case, the demarcation between the carcinomatous and sarcomatous components was distinct in all microscopic fields. Immunohistochemical analysis was negative for epithelial membrane antigen (EMA) and keratin in the sarcomatous component and was negative for desmin in the carcinomatous component, suggesting that this tumor could be derived from the two different stem cells. To determine the histogenesis of this tumor, both carcinomatous and sarcomatous lesions were microdissected from formalin-fixed tissues and DNAs were prepared by proteinase K digestion. PCR amplification of the human androgen receptor (HUMARA) short tandem repeat (STR), after Hpa II digestion of the genomic DNA, indicated that the patterns of X-chromosome inactivation were identical in both components. Moreover, both components contained the identical TGT --> TTT transversion in codon 275 of the p53 gene. These observations strongly support the hypothesis that this tumor is derived from a single totipotent stem cell.
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PMID:Carcinosarcoma of the breast: molecular-biological study for analysis of histogenesis. 982 16

Low-grade diffuse astrocytomas have an intrinsic tendency for malignant progression but the factors determining the kinetics of this process are still poorly understood. We report here the case of a male patient who developed a fibrillary astrocytoma at the age of 33 years and who underwent six surgical interventions over a period of 17 years without radiotherapy or chemotherapy. The first three biopsies spanned a period of 11 years and led to the diagnosis of low-grade, diffuse astrocytoma (WHO grade II), with a growth fraction (MIB-1 labeling index) of 2.3-3.7%. The fourth to sixth biopsies showed histological features of anaplastic astrocytoma (WHO grade III), with growth fractions between 5.0 and 10.5%. The fraction of gemistocytic neoplastic astrocytes also increased, from 0.3% in the first biopsy to 17.5% in the last biopsy and preceded the increase in proliferative activity and transition to anaplastic astrocytoma. The fraction of tumor cells immunoreactive to BCL-2 increased from 0.3% to 8.2%. A p53 mutation in codon 273 (CGT-->TGT, Arg-->Cys) was identified in the first biopsy and persisted throughout the course of the disease. However, the fraction of cells with p53 protein accumulation increased significantly during progression, from 3.2% in the first biopsy to 13.7% in the last. The absence of additional genetic alterations (PTEN mutations, loss of chromosome 10 and 19q) may be responsible for the slow progression and lack of glioblastoma features even after a 17-year disease duration.
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PMID:A case history of glioma progression. 1033 92

Although characterized by a highly variable phenotype and multiple genetic alterations, glioblastomas are considered monoclonal in origin. We here report on a 64-yr-old patient who developed a second glioblastoma in the left frontal lobe 10 yr after surgical resection of a glioblastoma of right frontal lobe. The first tumor contained 2 p53 mutations, in codon 213 (CGA-->TGA, Arg-->stop) and codon 306 (CGA-->TGA, Arg-->stop), further, 1 missense PTEN mutation (codon 257, TTC-->TTA, Phe-->Leu) and a silent PTEN mutation (codon 154, TTC-->TTT, Phe-->Phe). The second glioblastoma also contained multiple, but different mutations: p53 mutations in codons 158 (CGC-->CAC, Arg-->His) and 273 (CGT-->TGT, Arg-->Cys), and a PTEN mutation in codon 233 (CGA-->TGA, Arg-->Stop). Both neoplasms had a homozygous p16 deletion. The discordant pattern of mutations indicates that the second glioblastoma was not a recurrence but an independent second glioblastoma. The presence in these neoplasms of multiple mutations in tumor suppressor genes suggests the involvement of a novel disease mechanism but there was no indication of a DNA mismatch repair deficiency or of an inherited tumor syndrome.
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PMID:Second primary glioblastoma. 1127 8


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