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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When the causes of death were determined in 18 relations of a child with Fanconi's anaemia 10 deaths were found to be due to carcinoma of various organs. Cases of osteogenic sarcoma, leukaemia, and Marfan's syndrome were also discovered among relatives. The family was from a remote community in the hebrides and there was considerable intermarriage. Suggestive evidence of heterozygosity was found by chromosome analysis.
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PMID:Familial cancer on a Scottish island. 106 48

Mutations in the FBN1 gene, encoding the extracellular matrix protein fibrillin-1, result in the dominant connective tissue disease Marfan syndrome. Marfan syndrome has a variable phenotype, even within families carrying the same FBN1 mutation. Differences in gene expression resulting from sequence differences in the promoter region of the FBN1 gene are likely to be involved in causing this phenotypic variability. In this report, we present an analysis of FBN1 transcription start site (TSS) use in mouse and human tissues. We found that transcription of FBN1 initiated primarily from a single CpG-rich promoter which was highly conserved in mammals. It contained potential binding sites for a number of factors implicated in mesenchyme differentiation and gene expression. The human osteosarcoma line MG63 had high levels of FBN1 mRNA and secreted fibrillin-1 protein to form extracellular matrix fibres. The human embryonic kidney line HEK293 and two breast cancer lines MCF7 and MDA-MB-231 had levels of FBN1 mRNA 1000 fold lower and produced negligible amounts of fibrillin-1 protein. Therefore MG63 appears to be the optimal cell line for examining tissue-specific, biologically relevant promoter activity for FBN1. In reporter assays, the conserved promoter region was more active in MG63 cells than in non-FBN1-expressing lines but additional elements outside the proximal promoter are probably required for optimal tissue-specific expression. Understanding the regulation of the FBN1 gene may lead to alternative therapeutic strategies for Marfan syndrome.
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PMID:Experimental and bioinformatic characterisation of the promoter region of the Marfan syndrome gene, FBN1. 1957 90

Osteosarcoma is a malignant neoplasm of mesenchymal origin that is presumed to arise from osteoblasts. Considered a rare tumor, approximately 1000 cases of osteosarcoma are diagnosed in the United States each year, and osteosarcoma of the foot is rarer still. Marfan syndrome (MFS) is a rare genetic disorder that affects 1 in 5000 individuals and is caused by mutations in the fibrillin 1 (FBN1) gene. MFS phenotype affects several body systems, including soft connective tissue and bone. Here we report, for the first time, an individual with MFS that was treated for osteosarcoma. Surgically resected tissue was used to initiate an osteosarcoma cell line (PSU-OS-M) that exhibits attachment-independent growth and loss of contact inhibition in vitro. Genomic DNA was isolated from the tumor cells, and primers that anneal to intronic regions were used to amplify and sequence all 65 coding exons of the FBN1 gene. A two base pair insertion that results in a novel premature termination codon (PTC) was found in exon 52. Protein from the normal allele is detectable in PSU-OS-M cell-conditioned medium, but protein from the mutant allele was not detectable. Immunofluorescent microscopy demonstrates that PSU-OS-M cells can assemble fibrillin 1 microfibrils in culture, and fibronectin assembly is normal. As such, the PSU-OS-M cell line is to our knowledge the first oncogenically transformed cell line with a mutant fibrillin gene and may serve as a useful tool for studying molecular mechanisms of MFS and nonsense-mediated decay.
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PMID:Osteosarcoma in a Marfan patient with a novel premature termination codon in the FBN1 gene. 2067 86