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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple genome alterations can be seen within a tumor and continue to accumulate throughout development of the growth. Chromosome deletions occurring in tumors are generating much interest. To date, the best known model is retinoblastoma whose study gave rise to the concepts of anti-oncogene or tumor suppressor gene. Studies of genetic anomalies in colorectal tumors have led to an elegant model of colonic carcinogenesis in which multiple steps, each with its corresponding genetic anomaly, successively accumulate, with deletion of the p53 gene occurring as a late event. Successive anomalies of the p53 gene (mutations, deletions) occur during passage from a low-grade astrocytoma to a higher-grade astrocytoma. Studies of familial forms of breast cancer and of breast and ovarian cancer have also provided insight into the biology of these tumors, with the identification of a predisposing chromosomal area whose location is 17 q-12-21. These approaches open up possibilities for screening techniques and use of preventive treatments in highly selected patients. However they raise many ethical problems. There is a need for developing a charter for these family studies in the near future.
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PMID:[Genetics and cancers]. 130 91

The presence of mutations in the p53 gene was examined in ovarian cancers by a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. The primers were designed to amplify exons 5 through 9 that contain phylogenetically conserved domains of the p53 gene. Mutations were detected in 5 out of 10 cases, one of which contained a deletion in the second allele. A single base substitution was detected in 4 cases at codons 162, 175, 205 and 273 and a single base insertion in one case within codon 315. A high frequency of p53 mutations in ovarian cancers and lack of mutation in 6 benign ovarian tumors and 2 normal ovaries suggested that the mutation of the p53 gene was associated with the genesis and/or progression of ovarian cancer. In 1 of 7 endometrial cancers, two mutations at codons 239 and 254 were detected.
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PMID:Detection of p53 gene mutations in human ovarian and endometrial cancers by polymerase chain reaction-single strand conformation polymorphism analysis. 133 65

Genetic alterations of various cancers have been clarified by recent development of molecular biology. Multiple genetic alterations occur through the development of cancer. Both activation of proto-oncogenes and inactivation of tumor suppressor genes are important for the development of cancer. Alterations of oncogenes such as K-ras, c-erbB-2/HER-2/neu and c-myc, and those of tumor suppressor genes such as p53, RB and DCC have been reported in ovarian cancer. Allelic losses of the specific chromosomes, which suggest the existence of tumor suppressor genes on those chromosomes, also have been reported in ovarian cancer. Further studies on genetic alterations of ovarian cancer will clarify the mechanisms for the development of ovarian cancer and also will develop new methods for prevention, diagnosis and treatment in clinical.
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PMID:[Genetic alterations in the genesis and development of ovarian cancer]. 135 31

The discovery of cancer-causing genes has provided us with the exciting opportunity to begin to understand the molecular pathology of ovarian cancer. Activation of several of these genes including HER-2/neu, myc, ras, and p53 has been described in some ovarian cancers (Table 2). In addition, some proto-oncogenes such as the EGF receptor (erbB) and the M-CSF receptor (fms) are expressed along with their respective ligands in some ovarian cancers. Finally, for every oncogene that has been studied in ovarian cancer, there are at least a half-dozen that remain unexplored. In the future, when we have a better understanding of the molecular pathology involved in the development of ovarian cancer, this may allow us to better diagnose and treat, and eventually prevent, ovarian cancer.
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PMID:Oncogenes in ovarian cancer. 150 Mar 87

Tumorigenesis is a multistep process involving mutations of dominantly acting proto-oncogenes and mutations and loss-of-function mutations of tumor suppressor genes. Some of these mutations may be inherited, but most of them are acquired. Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers, such as colon cancer. In the case of ovarian cancer, relatively little is known about the genetic events associated with the initiation or subsequent progression and metastases of the tumor. Cytogenetic analysis has revealed a high incidence of both structural and numerical chromosome changes, and the extent of these changes seems to increase with tumor progression. Oncogene activations of the proto-oncogenes K-ras, c-myc and c-erbB-2 have been found more frequently in aggressive ovarian tumors and may be associated with poor survival. Tumor-specific allele loss involving putative tumor suppressor genes has been observed for loci at chromosomes 11p, 17p, and 17q,--loci commonly deleted in other cancers too. A relatively high incidence of allelic loss on chromosome 6q appears to be specific to ovarian carcinoma. Familial breast/ovarian cancer has been suggested to map to chromosome 8q. Recently we have found a germ-line mutation in the tumor suppressor gene p53 in a family with breast- and ovarian cancers, indicating that this is the predisposing gene in this family. Genetic changes important for the etiology of ovarian cancers seem to involve both somatic mutations of oncogenes and somatic or germ-line inactivation of tumor suppressor genes.
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PMID:Oncogenesis in ovarian cancer. 150 89

Familial clustering of breast cancer has been recognised for over a century but until recently a genetic basis has been suspected rather than proven. Epidemiological studies have tended to support the view that an autosomal dominant gene, with high but incomplete penetrance, accounts for most breast cancer families. However, it is likely that several different predisposing genes are present within most populations. Difficulties arise in a conventional 'linkage mapping' approach to identifying these genes, first, because it is not clear that genetically homogeneous groups of families can be recognised on the basis, for example, of mean age of onset or pattern of other cancers within the kindred and, second, because breast cancer is so common (affecting almost one in twelve women) that large affected kindreds are likely to include an admixture of sporadic (non-genetic) cases. Cytogenetic and 'Loss of Heterozygosity' (LOH) studies in sporadic breast cancers have pointed to several candidate loci for breast cancer genes but there is no clear consensus from these two approaches that might direct attention to any prime target region. Recent reports of tight linkage between familial breast cancer (early onset) and breast/ovarian cancer (regardless of mean age of onset) and a locus on chromosome 17q21 defined by the anonymous probe CMM86, have not been confirmed in detail but have led to the identification of a locus some 15 Mb centromeric of CMM86 that gives a high positive lod at very low recombination fraction in fifteen Edinburgh breast and breast/ovarian cancer families. The disease in the majority of such families therefore appears to be attributable to a mutant gene at 17q12-21. A much smaller proportion of familial breast cancer is accounted for by mutations in the p53 gene (17p13). Not all such families fulfil the criteria for Li-Fraumeni syndrome and not all of the inherited mutations lie within exon 7 of p53. Counselling of members of breast cancer families becomes more exacting as these genetic lesions are identified. It is essential to extend the collection of data and tissue (blood or fixed pathology material) as widely as possible to confirm linkage to a specific locus within each individual kindred, to define the precise mutation and to establish the cancer phenotype and its penetrance. In the course of these studies a substantial population of women at high risk of breast (and other) cancer will be identified. Resources should be directed to this population so that optimum procedures for screening and prevention can be developed.
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PMID:Familial breast cancer. 151 Nov 56

Ovarian cancers are often diagnosed at a late stage, after the cancer cells have spread to extraovarian sites. Failure to diagnose these tumors earlier may reflect the lack of symptoms and the need for a sensitive, reliable screening test. Alternatively, this can be explained by the hypothesis that some of the extraovarian tumor implants do not represent metastatic spread from the primary cancer but instead are multiple primary tumors developing simultaneously in the peritoneal epithelium. If this is the case, some patients with advanced ovarian cancer may never have had a stage I disease, making early detection theoretically impossible. In this study, we examined the mutational pattern of the p53 gene in 9 patients with epithelial ovarian cancers using tissue collected from different sites within the same patient. In all 9 cases, the mutational pattern of the p53 gene was identical in cancer cells from different sites within the same patient, strongly suggesting that these ovarian tumors were of unifocal origin and that cancer tissues collected from different sites are derived from a single origin.
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PMID:Unifocal origin of advanced human epithelial ovarian cancers. 151 69

The p53 locus on the short arm of chromosome 17 at 17p 13.1 was examined for loss of heterozygosity, mutation, mRNA and protein expression in 60 primary breast cancers. Allele loss around the p53 locus was detected in 19/45 informative tumours (42%). p53 mutations in the evolutionarily conserved exons 5 to 9 were detected in 17/60 (28%) by amplification mismatch and confirmed by direct DNA sequencing. p53 mRNA expression was detected by Northern blot in 36/59 (61%) of tumours, and p53 protein expression using antibody 1801 on frozen-tissue sections in 13/44 of the tumours examined. p53 mutation was significantly associated with oestrogen-receptor-poor tumours (p less than 0.01) and hence with poor prognosis, but not with other clinical or pathological parameters. There was no statistical correlation between loss of heterozygosity around the p53 locus at 17p13.1 and p53 mutation. Furthermore, p53 mutation was not associated with p53 expression detected by immunohistochemical staining with antibody 1801 or as p53 mRNA. In addition, events on 17p (allele losses, p53 mutation, p53 expression) were independent of c-erbB-2 expression. In breast cancer, by contrast with colorectal, lung and ovarian cancer, there appears to be no clear association between p53 DNA abnormalities and p53 expression.
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PMID:p53 allele losses, mutations and expression in breast cancer and their relationship to clinico-pathological parameters. 153 17

Hereditary breast cancer is common and accounts for approximately 10-14% of all breast cancers. Knowledge of a family history of breast cancer may significantly influence diagnosis and therapy. Genetic heterogeneity has been demonstrated in familial breast cancer. Recently inherited mutations in the tumor suppressor gene p53, have been shown to be the underlying defect in the Li-Fraumeni syndrome. We have shown that defects in this gene also play a role in the predisposition to other familial breast cancers. The gene responsible for early onset familial breast and ovary cancer has recently been mapped to chromosome 17q21. For most of the sporadic breast cancers a multifactorial model, including variable genetic and environmental factors, has been considered. Two genetic risk factors which may predispose for a considerable portion of breast cancers are the gene causing ataxia telangiectasia (AT) and the gene that gives rise to proliferative breast disease (PBD). Identification of distinct genes enhancing the risk of breast cancer will give us the opportunity to identify high risk individuals. Such individuals may benefit from periodic examination affording the possibility of early diagnosis and treatment.
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PMID:Role of genetic factors in breast cancer susceptibility. 162 29

In an effort to analyze molecular mechanisms of human ovarian carcinogenesis, we studied the structure and expression of the p53 gene in different cell lines established from human ovarian carcinomas. In all six lines (PA-1, Caov-3 and -4, OVCAR-3, SK-OV-3, and Kuramochi), p53 abnormalities were detected. In the SK-OV-3 cell line, Southern analysis suggested the presence of sequence deletions/rearrangements in at least one allele of the p53 gene, and transcripts were not detectable by either Northern or polymerase chain reaction analysis. Sequence analysis of the entire coding region of the p53 gene revealed point mutations resulting in codon changes of a highly conserved region of the protein in four cell lines, Caov-3 and -4, OVCAR-3, and Kuramochi. In the Caov-3 cell line, the point mutation resulted in chain termination at codon 136. Quantitation of p53 protein by immunoprecipitation analysis revealed a 6-fold higher than control cell level in PA-1. By contrast, p53 protein was not detectable in lines Caov-3 and SK-OV-3. We conclude that altered levels of p53 gene expression and/or mutant forms of the p53 gene product are associated with all human ovarian cancer cells tested.
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PMID:Abnormal structure and expression of the p53 gene in human ovarian carcinoma cell lines. 163 34


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