Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with bilateral retinoblastoma and subsequent multiple primary osteosarcomas has been described previously. Osteosarcoma cell lines established from this patient were shown to express a shortened RB1 mRNA transcript and no detectable normal Rb protein. We now show that the osteosarcoma cell lines have lost one TP53 allele and contain a mutation in exon 8 codon 286 [GAA to AAA (Glu to Lys)] in the remaining allele. Consequently, the osteosarcoma cell lines have no normal Rb protein and no normal p53 protein. Neither constitutional DNA nor DNA extracted from a retinoblastoma of the left eye of the patient contained the TP53 mutation, suggesting that the TP53 mutation in the osteosarcoma cells may represent a tumor-promoting mutation, which confers a selective growth advantage. If both RB1 and TP53 are involved in the initiation of osteosarcoma, the mechanisms for development of the retinoblastoma and osteosarcoma tumors are different.
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PMID:A TP53 mutation detected in cells established from an osteosarcoma, but not in the retinoblastoma of a patient with bilateral retinoblastoma and multiple primary osteosarcomas. 133 9

A malignant stromal tumor of the testis with an osteosarcoma component and five of its metastases mainly containing osteosarcoma have been analyzed for RB1 and TP53 abnormalities. Whereas in the primary tumor and in some of the metastases loss of heterozygosity could not be detected for RB1 or for the 17p13 region in which TP53 is located, other metastases showed such losses of heterozygosity. By polymerase chain reaction analysis an 18-base pair deletion from exon 5 of the TP53 gene was found in a small proportion of primary tumor cells and in one of the metastases, but not in the other metastases. Therefore, in this case neither RB1 nor TP53 seems to play an essential role in the initiation of osteosarcoma.
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PMID:Analysis of a metastasizing testicular mixed gonadal stromal tumor with osteosarcoma components suggests that a malignant tumor with the histology of osteosarcoma may develop without primary involvement of RB1 and TP53. 142 18

We analyzed 14 native osteosarcoma tissue samples for alterations of the tumor suppressor genes RB1 and p53 on the DNA level, and as far as possible, the RNA level. Southern blot analyses concerning both tumor suppressor genes were carried out in all osteosarcomas. In two cases we could demonstrate a deletion within the RB1 gene. DNA analysis of a third osteosarcoma patient revealed a rearrangement of the p53 gene. We had the opportunity of performing corresponding northern analyses in eight native osteosarcoma specimens. The RB1 gene expression was significantly decreased or completely absent in six tumor samples. In two of these tissue probes the expression of both tumor suppressor genes was missing. We determined coexistence of decreased expression of both tumor suppressor genes in one additional case. In summary, 7/14 or 6/8 cases of osteosarcomas (including only those cases which allowed both analyses) showed RB1 gene alteration. In 3/14 or 3/8 osteosarcomas we could determine p53 gene abnormalities. This may indicate that either loss of p53 function is etiologically important only for the development of some osteosarcomas, or a major part of p53 gene mutations are subtle ones and their detection requires more sophisticated techniques, which are currently under development.
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PMID:Studies of the RB1 gene and the p53 gene in human osteosarcomas. 152 85

Osteosarcoma tumorigenesis is consistent with a model by which tumorigenesis results if both alleles at the retinoblastoma susceptibility locus (RBI) are altered. Additional genetic evidence strongly suggests that another obligate event in osteosarcoma tumorigenesis is the homozygous alteration of another gene, p53. Both the RB1 gene and p53 have been proposed to act as tumor-suppressor genes, suggesting that, in this instance, tumorigenesis is the result of the loss of gene function of these two genes, rather than a gain of function.
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PMID:Molecular genetic considerations in osteosarcoma. 167 82

In addition to retinoblastoma and osteosarcoma, mutation of both alleles of the RB1 gene occurs frequently in several other types of tumors. In order to evaluate the role of RB1 in cancer, the wild type RB1 gene was introduced into the RB1-deleted breast cancer cell line MDA-468-S4 and retinoblastoma cell lines WERI-Rb1 and Y-79. The RB1 complementary DNA was under control of the inducible murine metallothionein promoter in MDA-468-S4 and the thymidine kinase promoter in the retinoblastoma lines. The protein, p110RB1, produced from the exogenously introduced gene appeared normal by immunoprecipitation, Western blot analysis, and nuclear localization and also showed normal cell cycle-dependent phosphorylation and an ability to bind to E1a protein. No changes in growth rate or morphology were observed in either of the reconstituted cell types. Expression of p110RB1 in MDA-468-S4 did not affect anchorage-independent growth when measured by colony formation in soft agar. Although the ability of WERI-Rb1 cells expressing p110RB1 to form colonies in methylcellulose was reduced, the reconstituted retinoblastoma cell lines formed intraocular tumors in immunodeficient mice with the same efficiency as the RB1-negative parent cell lines and the tumors produced by the RB1-reconstituted cells continued to express p110RB1. These experimental results suggest that the malignant phenotype is little affected by the replacement of p110RB1 and that RB1 is a relatively weak tumor suppressor gene.
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PMID:Failure of RB1 to reverse the malignant phenotype of human tumor cell lines. 173 54

We have examined the functional consequences of mutations present in defective alleles of the retinoblastoma susceptibility gene (RB1) isolated from two spontaneously arising tumors. Unlike cDNA clones expressing the wild-type protein p110Rb, those encoding the two mutant proteins failed to induce the appearance of senescent cells in transfected Saos-2 human osteosarcoma cells. The mutant proteins were also defective in binding to the E1A oncoprotein, were unable to become hyperphosphorylated, and failed to become tightly associated with nuclear structures. We conclude that mutations in two distinct regions of the protein concomitantly affect these four aspects of p110Rb function.
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PMID:Nonfunctional mutants of the retinoblastoma protein are characterized by defects in phosphorylation, viral oncoprotein association, and nuclear tethering. 182 60

The retinoblastoma (RB1) gene is a ubiquitously expressed gene encoding a cell-cycle control protein. Inactivation of this gene plays a crucial role in the development of retinoblastoma, osteosarcoma, and other tumors. In a search for structurally related gene sequences we identified a 5.5-kb BamHI fragment strongly cross-hybridizing with the 5' end of the RB1 cDNA. Molecular cloning, in situ hybridization, restriction mapping, and sequence analysis identified this DNA segment as the 28S rRNA gene. The absence of other cross-hybridizing sequences suggests that the RB1 gene is not part of a structurally related gene family.
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PMID:No evidence for sequences structurally related to the RB1 gene in the human genome. 199 43

Mutations of the retinoblastoma (RB1) gene are not confined to retinoblastoma, but are also involved in the development of osteosarcoma. Structural aberrations within the RB1 gene have been studied in fresh samples of eleven cases of osteosarcoma. In five cases a rearrangement was detected, one of which was best explained as a partial duplication. The chromosomal mechanisms by which the nonmutated RB1 allele was lost appeared to be similar in frequency to those that have been reported for retinoblastoma. Loss of heterozygosity was observed for chromosomes 3, 11, 13, 17, and 22. However, when no loss of heterozygosity of chromosome 13 was detected, the other chromosomes retained their heterozygosity as well. A complete association of loss of heterozygosity of chromosomes 13 and 17 was observed. This can be taken as an indication of the involvement of another tumor suppressor gene at chromosome 17 in the initiation of osteosarcoma.
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PMID:Complete association of loss of heterozygosity of chromosomes 13 and 17 in osteosarcoma. 203 39

The event triggering malignant proliferation in 70% of retinoblastoma tumours is loss of heterozygosity for chromosome 13q14, whereby the normal retinoblastoma gene (RB1) allele is lost and an already mutated RB1 allele remains in the tumour. The first allele suffers a mutational event--deletion, duplication or point mutation (manuscript in preparation)--either in the germ line (all bilateral patients) or in a somatic retinal cell (most unilateral patients). Most bilateral patients have no family history of retinoblastoma and are presumed to have new germline mutations which arose in the egg, sperm or early embryo. We have determined the parental origin of the retained allele in nine retinoblastoma tumours from eight unrelated non-familial cases by using RB1-linked genetic markers. Six tumours retained the paternal allele and three retained the maternal allele. Of the three unilateral tumours, only one retained the paternal RB1 allele. Thus, there is no evidence that the paternal RB1 allele is preferentially retained in retinoblastoma, as has been suggested to be the case in osteosarcoma. By contrast, tumours from four of the five bilateral patients retained the paternal RB1 allele. This suggests either that new germline RB1 mutations arise more frequently during spermatogenesis than during oogenesis, or that imprinting in the early embryo affects chromosomal susceptibility to mutation.
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PMID:Preferential germline mutation of the paternal allele in retinoblastoma. 256 88

In order to assess the involvement of the 13q14 region in the development of osteosarcoma, both osteosarcoma tumor cells and normal tissue from a retinoblastoma patient previously used in restriction fragment length polymorphism studies, and sarcoma cells and normal fibroblasts from other tumor patients, have been investigated with respect to esterase D (E.C. 3.1.1.1) expression and chromosome pattern. In spite of an increased number of apparently normal chromosomes #13, a 50% reduction in esterase D activity in osteosarcoma cells from the retinoblastoma patient was observed. This suggests that loss of the RB1 gene or an OSRC gene closely linked to the ESD and RB1 gene loci is involved in the development of the osteosarcoma tumor. No reduction in esterase D expression was seen in four other sarcoma cell lines.
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PMID:Chromosome 13 instability and esterase D expression in an osteosarcoma cell line. 287 16


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