Osteosarcoma development and stem cell differentiation.
Osteosarcoma is the most common nonhematologic malignancy of bone in children and adults. The peak incidence occurs in the second decade of life, with a smaller peak after age 50. Osteosarcoma typically arises around the growth plate of long bones. Most osteosarcoma tumors are of high grade and tend to develop pulmonary metastases. Despite clinical improvements, patients with metastatic or recurrent diseases have a poor prognosis. Here, we reviewed the current understanding of human osteosarcoma, with an emphasis on potential links between defective osteogenic differentiation and bone tumorigenesis. Existing data indicate osteosarcoma tumors display a broad range of genetic and molecular alterations, including the gains, losses, or arrangements of chromosomal regions, inactivation of tumor suppressor genes, and the deregulation of major signaling pathways. However, except for p53 and/or RB mutations, most alterations are not constantly detected in the majority of osteosarcoma tumors. With a rapid expansion of our knowledge about stem cell biology, emerging evidence suggests osteosarcoma should be regarded as a differentiation disease caused by genetic and epigenetic changes that interrupt osteoblast differentiation from mesenchymal stem cells. Understanding the molecular pathogenesis of human osteosarcoma could ultimately lead to the development of diagnostic and prognostic markers, as well as targeted therapeutics for osteosarcoma patients.
Tang
Ni
N
The Second Affiliated Hospital and the Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
Song
Wen-Xin
WX
Luo
Jinyong
J
Haydon
Rex C
RC
He
Tong-Chuan
TC
D001859:Bone Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D002454:Cell Differentiation / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D016518:Neurofibromatosis 2 / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000503:physiopathology*; D011519:Proto-Oncogenes / Q000235:genetics; D053484:RecQ Helicases / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D053484:RecQ Helicases