Osteosarcoma: Molecular Pathogenesis and iPSC Modeling

Trends Mol Med. 2017 Aug;23(8):737-755. doi: 10.1016/j.molmed.2017.06.004. Epub 2017 Jul 20.

Abstract

Rare hereditary disorders provide unequivocal evidence of the importance of genes in human disease pathogenesis. Familial syndromes that predispose to osteosarcomagenesis are invaluable in understanding the underlying genetics of this malignancy. Recently, patient-derived induced pluripotent stem cells (iPSCs) have been successfully utilized to model Li-Fraumeni syndrome (LFS)-associated bone malignancy, demonstrating that iPSCs can serve as an in vitro disease model to elucidate osteosarcoma etiology. We provide here an overview of osteosarcoma predisposition syndromes and review recently established iPSC disease models for these familial syndromes. Merging molecular information gathered from these models with the current knowledge of osteosarcoma biology will help us to gain a deeper understanding of the pathological mechanisms underlying osteosarcomagenesis and will potentially aid in the development of future patient therapies.

Keywords: cancer etiology; familial cancer syndrome; induced pluripotent stem cell; osteosarcoma.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / metabolism
  • Bone Neoplasms* / pathology
  • Humans
  • Induced Pluripotent Stem Cells* / metabolism
  • Induced Pluripotent Stem Cells* / pathology
  • Li-Fraumeni Syndrome* / genetics
  • Li-Fraumeni Syndrome* / metabolism
  • Li-Fraumeni Syndrome* / pathology
  • Models, Biological*
  • Osteosarcoma* / genetics
  • Osteosarcoma* / metabolism
  • Osteosarcoma* / pathology