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

The clonality of disseminated serous carcinoma involving the ovary, peritoneum, and, occasionally, the endometrium is controversial. Histopathologic examination alone cannot unequivocally distinguish between a monoclonal origin and a multicentric origin. Two patients with peritoneal serous carcinoma with minimal ovarian involvement (one with endometrial serous carcinoma), nine patients with stage III bilateral ovarian carcinoma, and one patient with stage III bilateral carcinosarcoma were studied for clonality. One patient with ovarian carcinoma that recurred after chemotherapy was also studied. Previous analyses of single frozen tumor specimens from these patients had identified different p53 gene mutations in each patient. To test the hypothesis that the disseminated cancers had a monoclonal origin, we assayed DNA from numerous foci from each patient to determine whether the known p53 mutation was present in each specimen. Identical mutations were detected in the tumor foci from each patient with peritoneal dissemination and minimal ovarian involvement, including one patient with an endometrial serous carcinoma as well. In all the patients with bilateral ovarian cancer, the genetic change in p53 was identical in both ovarian tumors. Genetic progression was observed in two patients, one of whom showed a loss of heterozygosity involving the p53 gene in a recurrent tumor. In the second patient, a p53 mutation not present in either ovarian tumor was detected in a metastatic tumor from the omentum. These results strongly suggest that disseminated serous carcinomas, whether primary in the ovary, endometrium, or peritoneum, are of monoclonal rather than multicentric origin; that bilateral stage III ovarian cancers are typically of monoclonal origin; and that additional genetic events involving p53 might occur during progression of these tumors.
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PMID:Ovarian, peritoneal, and endometrial serous carcinoma: clonal origin of multifocal disease. 868 9

The usefulness of prognostic factors in gynecological cancer was evaluated using the oncogenes, tumor suppressor genes and DNA viruses detected with the molecular biological technique. In uterine cervical cancer, HPV types 16 and 18 are considered to have a high oncogenic risk, and are commonly associated with high grade CIN and invasive cancer under persistent HPV infection. C-myc overexpression in advanced stage and p53 mutation in HPV negative case are associated with poor survival. In endometrial cancer, oncogene activation and expression are less frequent than in cervical and ovarian cancer. K-ras point mutation (codon 12) tumors are more aggressive and c-erbB-2 overexpression are associated with metastasis and poor survival. In ovarian cancer, there are numerous abnormalities of oncogenes and tumor suppressor genes. Especially, EGF-R and PDGF-R alpha expression are associated with decreased survival. p53 mutation also decreases survival and response to chemotherapy. Recently. MSH2 (Lynch II syndrome) and BRCA1 gene are known to relate with familial ovarian cancer.
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PMID:[Evaluation of prognostic factors in gynecological cancer examined by molecular biological study]. 868 14

Approximately 20% of breast cancer patients have a family history of the disease, and in one-fourth of these cases breast cancer appears to be inherited as an autosomally dominant trait. Five genes and gene regions involved in breast cancer susceptibility have been uncovered. Germ-line mutations in the recently cloned BRCA1 gene at 17q21 is considered to be responsible for the disease in a majority of the breast-ovarian cancer families and in 40-45% of the site-specific breast cancer families, but appears not to be involved in families with both male and female breast cancer cases. The BRCA2 locus at 13q12-q13 appears to be involved in 40-45% of the site-specific breast cancer families, and in most of the families with affected males. The gene located in this region, however, does not seem to confer susceptibility to ovarian cancer. The TP53 gene is involved in breast cancer development in the Li-Fraumeni syndrome and Li-Fraumeni syndrom-like families, whereas germ-line mutations in the androgen receptor (AR) gene is present in a subset of male breast cancers. Furthermore, females who are obligate carriers of ataxia telangiectasia (AT) have a 4-12 times relative risk of developing breast cancer as compared with the general female population, indicating that germ-line mutations in AT also confer susceptibility to breast cancer.
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PMID:Genetic heterogeneity in breast cancer susceptibility. 869 52

A new cell line, SR8, and xenograft model of ovarian carcinoma has been established in this laboratory over the past 20 months from a patient with advanced ovarian cancer. Electron microscopic examination of SR8 cells demonstrated the presence of desmosomes and tonofilaments; SR8 cells expressed epithelial membrane antigen (EMA) and glandular associated cytokeratin, all of these confirmed the epithelial origin of this cell line. In addition, SR8 cells expressed CA125, as did the original ovarian tumour. EGF-R and TP53 expression was identified by immunocytochemistry (ICC) in this line. Nearly all the SR8 cells (93%) expressed HLA-class I antigen while 13.5% expressed HLA-DR. SR8 cells showed near-diploid and -triploid chromosome populations with several clonal and non-clonal rearrangements. Subcutaneous and intraperitoneal xenografting of SR8 cells resulted in invasive tumour production at both sites in 3/4 and 4/4 female nude mice, respectively. These xenografts exhibited similar morphology as that of original tumour and were found to express EMA, cytokeratin, CA125 and TP53. The potential research applications of this cell line are discussed.
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PMID:SR8--the establishment and characterisation of a new ovarian carcinoma cell line and xenograft model. 869 26

Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was identified in a late onset breast cancer family (kindred Lund 5; mean age 58 years) using single stranded conformation polymorphism and sequence analysis. The mutation (a CCG to CTG transition) at codon 82 in exon 4, resulting in a proline to leucine substitution, has not previously been reported and was not present in a control set of 60 healthy individuals. Three of five woman with breast cancer (45, 57 and 65 years) were carriers of the alteration. Loss of heterozygosity at the p53 locus was not seen in the primary tumors of these women, but appeared as a partial loss of the wildtype allele in subsequent recurrent lesions of two gene carriers. The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation. Although it seems unlikely that the p53 germline mutation is the major cause of disease predisposition in Lund 5, the data suggest that some p53 alteration may confer a subtle influence on breast cancer development and progression.
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PMID:A novel p53 germline alteration identified in a late onset breast cancer kindred. 871 Mar 80

Identification of inherited cancer-predisposing genes offers opportunities for cancer prevention. Inherited susceptibility genes have been identified, primarily through studies of unusual cancer cases and families but also through general population studies. Examples include the RB1 gene for retinoblastoma; the WT1 gene for Wilms' tumor; germline p53 mutations in families with the Li-Fraumeni syndrome; the NF1 and NF2 genes for neuroblastomatosis, types 1 and 2; the VHL gene for renal cancer and other tumors associated with Von Hippel-Lindau disease; the APC gene for adenomatous polyposis coli; the BRCA1 gene for hereditary breast and ovarian cancer; and the mismatch repair genes for colon and other common cancers. For some cancers, identification of gene carriers might be beneficial for targeting screening and chemopreventive interventions. On the other hand, predisposition testing for cancer has the potential for harm from loss of insurability and employability, psychological distress, social stigmatization and other adverse effects. Research is needed to identify predisposition testing procedures that maximize benefits while minimizing harm to subjects. Chemoprevention trials in genetically susceptible populations offer the prospect of finding effective methods of reducing future cancer risk.
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PMID:Identification and management of inherited cancer susceptibility. 874 2

More than 90% of epithelial ovarian cancers arise from single cells. Malignant transformation can be associated with a number of molecular alterations including upregulation of tyrosine kinases and phosphatases, physiologic activation o ras, mutation of p53, amplification of myc, and increased activity of matrix metalloproteinases 2 and 9. Proliferation of transformed epithelial cells can be enhanced through the persistence of autocrine growth stimulation by TGF-alpha, loss of autocrine growth inhibition by TGF-beta, as well as paracrine growth stimulation by macrophage derived cytokines and OCAF, a novel lyso-phospholipid. Ascites tumor cells retain responsiveness to growth inhibition by TGF-beta which induces apoptosis in malignant ovarian epithelial cells, but not in normal ovarian surface epithelium. Proliferation of surface epithelial cells following ovulation may contribute to the pathogenesis of ovarian cancer. Use of oral contraceptives that suppress ovulation has been associated with reduced risk of ovarian cancer in later life. Retinoids also deserve further evaluation for chemoprevention. Treatment with fenretinide was associated with decreased incidence of ovarian cancer. Additive or synergistic inhibition of ovarian tumor cell proliferation has been observed with TGF-beta in combination with all-trans-retinoic acid. Early detection of ovarian cancer could improve survival. Transvaginal sonography (TVS) and serum markers such as CA-125 have been evaluated in multiple clinical trials. The former lacks adequate specificity, whereas the latter is not sufficiently sensitive. Use of multiple serum markers can improve sensitivity. A combination of CA-125, M-CSF and OVX-1 has detected > 95% of Stage I ovarian cancers. If similar results are obtained with different data sets, multiple serum markers could be used to trigger the performance of TVS, providing a potentially cost effective screening strategy. Prospective trials will be required to demonstrate that screening for early stage ovarian actually impacts on survival.
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PMID:Molecular approaches to prevention and detection of epithelial ovarian cancer. 874 99

Alterations in specific oncogenes and tumor suppressor genes that serve as surrogate markers of malignant transformation have been identified in ovarian cancers. Overexpression of the HER-2/neu oncogene occurs in approximately 30% of breast and ovarian cancers. In most studies, HER-2/neu overexpression has correlated with poor survival. Although mutation of the K-ras oncogene has been found in some mucinous ovarian cancers, mutations in this gene appear to be more common in borderline ovarian tumors. Amplification of c-myc occurs in approximately 30% of ovarian cancers and is more frequently seen in serous cancers. Mutation of the p53 tumor suppressor gene, with resultant overexpression of mutant p53 protein, occurs in 50% of Stage III/IV and 15% of Stage I/II ovarian cancers. Most p53 mutations in ovarian cancers are transitions, which suggests that they arise spontaneously rather than due to exogenous carcinogens. In contrast to the acquired genetic alterations described above that are a feature of sporadic ovarian cancers, a small fraction of epithelial ovarian cancers arise due to inherited genetic defects. Recently, the BRCA1 tumor suppressor gene on chromosome 17q was identified and shown to be responsible for some cases of hereditary breast and ovarian cancer. Families in which mutations in this gene exist are usually characterized by early age of disease onset. Presently, it remains unclear what fraction of hereditary ovarian cancers are due to BRCA1 mutations.
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PMID:Biomarkers in the ovary. 874

The aim of this investigation was to explore the relationships between p53 mutation, DNA aneuploidy, 17p deletions, and clinical stage in ovarian cancer. Nuclear suspensions were obtained by tissue disaggregation, stained with propidium iodide, and analysed on a Coulter EPICS Elite flow cytometer. DNA cell cycle analysis was performed using Multicycle software (Phoenix Flow Systems). DNA extracted from paraffin-embedded archival carcinomas/non-tumour tissue was used as template for PCR amplification of the microsatellite dinucleotide repeat polymorphism D17S513, a locus telomeric to p53 on 17p13.1. Allele loss at D17S513 was detected in 64.5 per cent of carcinomas (20 of 31 informative cases). DNA aneuploidy was detected in 20 of 54 (37 per cent) carcinomas. Eight of ten cases previously shown to harbour p53 mutations showed aneuploid DNA content. Although ten other DNA aneuploid cases had shown no p53 mutations, the results show a statistically significant association between p53 mutation and DNA aneuploidy (P < 0.01). Furthermore, the mean DNA index of the DNA aneuploid cases was significantly higher in p53 mutant cases compared with those showing no p53 mutation (P = 0.02). There was also a significant association between p53 mutations and stage, between ploidy and stage, and between allelic deletions at D17S513 or p53 and stage, but not between these allelic deletions and ploidy. p53 mutations appear to be associated with DNA aneuploidy in ovarian cancer independently of 17p deletions. p53 mutations, DNA aneuploidy, and 17p deletions are associated with late stage.
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PMID:p53 mutation, allele loss on chromosome 17p, and DNA content in ovarian carcinoma. 875 10

Endometriosis is a very common gynecological condition in which tissue similar to endometrium proliferates at sites outside the uterine cavity, most commonly the ovary. Although it generally remains a benign condition, malignant transformation has been documented. and it is commonly found in association with endometrioid subtype ovarian cancer. Tumor suppressor genes are commonly altered in ovarian cancers, and the development of endometriosis may involve mutations in the same class of genes. We have investigated this possibility by examining DNA from 40 cases of endometriosis for clonal status, alterations in TP53 and RASK, and allelic losses at candidate ovarian tumor suppressor loci on chromosome arms 6q, 9p, l1q, 17p, l7q, and 22q. The majority of endometriotic cysts were monoclonal, but interestingly, 8 of 10 normal endometrial glands were also monoclonal, demonstrating that both are able to develop from a single progenitor cell. No mutations were detected in TP53 or RASK. Loss of heterozygosity (LOH) was detected on chromosomes 9p (18%), 1lq (18%), and 22q (15%). In total, 11 of 40 (28%) cases demonstrated LOH at one or more of these loci. This study, which is the first to report LOH in endometriosis, supports the notion that tumor suppressor gene inactivation may play a role in the development of at least a subset of cases.
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PMID:Microsatellite analysis of endometriosis reveals loss of heterozygosity at candidate ovarian tumor suppressor gene loci. 875 23


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