Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone (GCT). We performed whole-exome sequencing in a large family with 14 PDB-affected members, four of whom developed GCT at multiple pagetic skeletal sites, and we identified the c.2810C>G (p.Pro937Arg) missense mutation in the zinc finger protein 687 gene (ZNF687). The mutation precisely co-segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated individuals with GCT associated with PDB (GCT/PDB) identified the same mutation in all individuals, unravelling a founder effect. ZNF687 is highly expressed during osteoclastogenesis and osteoblastogenesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB. Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk.
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PMID:ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor. 2684 10

Paget's disease of bone (PDB) is a chronic and focal bone disorder, characterized by increased osteoclast-mediated bone resorption and a subsequent compensatory increase in bone formation, resulting in a disorganized mosaic of woven and lamellar bone at one or more affected skeletal sites. As a result, bone pain, noticeable deformities, arthritis at adjacent joints, and fractures can occur. In a small proportion of cases neoplastic degeneration in osteosarcoma, or, less frequently, giant cell tumor has been also described at PDB sites. While recent epidemiological evidences clearly indicate a decrease in the prevalence and the severity of PDB, over the past 2 decades there have been consistent advances on the genetic mechanisms of disease. It is now clear that PDB is a genetically heterogeneous disorder, with mutations in at least two different genes (SQSTM1, ZNF687) and more common predisposing variants. As a counterpart to the genetic hypothesis, the focal nature of lesions, the decline in prevalence rates, and the incomplete penetrance of the disease among family members suggest that one or more environmental triggers may play a role in the pathophysiology of PDB. The exact nature of these triggers and how they might interact with the genetic factors are less understood, but recent experimental data from mice models suggest the implication of paramixoviral infections. The clinical management of PDB has also evolved considerably, with the development of potent aminobisphosphonates such as zoledronic acid which, given as a single intravenous infusion, now allows a long-term disease remission in the majority of patients.
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PMID:Paget's Disease of Bone. 3067 90