Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522083 (Osteosarcoma)
 2,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma is a devastating but rare disease, whose study has illuminated both the basic biology and clinical management of cancer over the past 30 years. These contributions have included insight into the roles of key cancer genes such as the retinoblastoma tumor suppressor gene and TP53, the identification of familial cancer syndromes implicating DNA helicases, and dramatic improvements in survival by the use of adjuvant chemotherapy. This review provides a synoptic overview of our current understanding of the molecular causes of osteosarcoma, and suggests future directions for study.
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PMID:Molecular pathogenesis of osteosarcoma. 1726 92

Osteosarcoma is the most common primary malignant tumor of bone. Analysis of familial cancer syndromes and sporadic cases has strongly implicated both p53 and pRb in its pathogenesis; however, the relative contribution of these mutations to the initiation of osteosarcoma is unclear. We describe here the generation and characterization of a genetically engineered mouse model in which all animals develop short latency malignant osteosarcoma. The genetically engineered mouse model is based on osteoblast-restricted deletion of p53 and pRb. Osteosarcoma development is dependent on loss of p53 and potentiated by loss of pRb, revealing a dominance of p53 mutation in the development of osteosarcoma. The model reproduces many of the defining features of human osteosarcoma including cytogenetic complexity and comparable gene expression signatures, histology, and metastatic behavior. Using a novel in silico methodology termed cytogenetic region enrichment analysis, we demonstrate high conservation of gene expression changes between murine osteosarcoma and known cytogentically rearranged loci from human osteosarcoma. Due to the strong similarity between murine osteosarcoma and human osteosarcoma in this model, this should provide a valuable platform for addressing the molecular genetics of osteosarcoma and for developing novel therapeutic strategies.
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PMID:Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. 1855 81

It has been difficult to identify the molecular features central to the pathogenesis of osteosarcoma owing to a lack of understanding of the cell or origin, the absence of identifiable precursor lesions, and its marked genetic complexity at the time of presentation. Interestingly, several human genetic disorders and familial cancer syndromes, such as Li-Fraumeni syndrome, are linked to an increased risk of osteosarcoma. Association of these same genetic alterations and osteosarcoma risk have been confirmed in murine models. Osteosarcoma is associated with a variety of genetic abnormalities that are among the most commonly observed in human cancer; it remains unclear, however, what events initiate and are necessary to form osteosarcoma. The availability of new resources for studying osteosarcoma and newer research methodologies offer an opportunity and promise to answer these currently unanswered questions. Even in the absence of a more fundamental understanding of osteosarcoma, association studies and preclinical drug testing may yield clinically relevant information.
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PMID:Osteosarcoma. 2020 69

Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, which include Rothmund-Thomson Syndrome in particular. These disorders have highlighted the important roles of P53 and RB respectively, in the development of osteosarcoma. The association of OS with RECQL4 mutations is apparent but the relevance of this to OS is uncertain as mutations in RECQL4 are not found in sporadic OS. Application of the knowledge or mutations of P53 and RB in familial and sporadic OS has enabled the development of tractable, highly penetrant murine models of OS. These models share many of the cardinal features associated with human osteosarcoma including, importantly, a high incidence of spontaneous metastasis. The recent development of these models has been a significant advance for efforts to improve our understanding of the genetics of human OS and, more critically, to provide a high-throughput genetically modifiable platform for preclinical evaluation of new therapeutics.
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PMID:Genetically engineered mouse models and human osteosarcoma. 2303 72