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.