Osteosarcoma in a Marfan patient with a novel premature termination codon in the FBN1 gene

Adriana Roopnariane, Robert J. Freed, Shawn Price, Edward Fox, Timothy M. Ritty

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)157-165
Number of pages9
JournalConnective Tissue Research
Volume52
Issue number2
DOIs
StatePublished - Apr 1 2011

Fingerprint

Nonsense Codon
Osteosarcoma
Marfan Syndrome
Genes
Cells
Tumors
Exons
Tissue
Alleles
Osteoblasts
Contact Inhibition
Microfibrils
Mutant Proteins
Conditioned Culture Medium
Cell Line
Neoplasms
Transformed Cell Line
Fibronectins
Inborn Genetic Diseases
Microscopic examination

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Biochemistry
  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Roopnariane, Adriana ; Freed, Robert J. ; Price, Shawn ; Fox, Edward ; Ritty, Timothy M. / Osteosarcoma in a Marfan patient with a novel premature termination codon in the FBN1 gene. In: Connective Tissue Research. 2011 ; Vol. 52, No. 2. pp. 157-165.
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Osteosarcoma in a Marfan patient with a novel premature termination codon in the FBN1 gene. / Roopnariane, Adriana; Freed, Robert J.; Price, Shawn; Fox, Edward; Ritty, Timothy M.

In: Connective Tissue Research, Vol. 52, No. 2, 01.04.2011, p. 157-165.

Research output: Contribution to journalArticle

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