Mutation Screening of the TNFRSF11A Gene Encoding Receptor Activator of NFkB (RANK) in Familial and Sporadic Paget's Disease of Bone ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-03

AUTHORS

A.B. Sparks, S.N. Peterson, C. Bell, B.J. Loftus, L. Hocking, D.P. Cahill, F.J. Frassica, E.A. Streeten, M.A. Levine, C.M. Fraser, M.D. Adams, S. Broder, J.C. Venter, K.W. Kinzler, B. Vogelstein, S.H. Ralston

ABSTRACT

Paget's disease of bone (PDB) is a common disorder characterized by focal areas of increased and disorganized osteoclastic bone resorption, leading to bone pain, deformity, pathological fracture, and an increased risk of osteosarcoma. Genetic factors play an important role in the pathogenesis of Paget's disease. In some families, the disease has been found to be linked to a susceptibility locus on chromosome 18q21-22, which also contains the gene responsible for familial expansile osteolysis (FEO)--a rare bone dysplasia with many similarities to Paget's disease. Insertion mutations of the TNFRSF11A gene encoding Receptor Activator of NF kappa B (RANK) have recently been found to be responsible for FEO and rare cases of early onset familial Paget's disease. Loss of heterozygosity (LOH) affecting the PDB/FEO critical region has also been described in osteosarcomas suggesting that TNFRSF11A might also be involved in the development of osteosarcoma. In order to investigate the possible role of TNFRSF11A in the pathogenesis of Paget's disease and osteosarcoma, we conducted mutation screening of the TNFRSF11A gene in patients with familial and sporadic Paget's disease as well as DNA extracted from Pagetic bone lesions, an osteosarcoma arising in Pagetic bone and six osteosarcoma cell lines. No specific abnormalities of the TNFRSF11A gene were identified in a Pagetic osteosarcoma, the osteosarcoma cell lines, DNA extracted from Pagetic bone lesions, or DNA extracted from peripheral blood in patients with familial or sporadic Paget's disease including several individuals with early onset Paget's disease. These data indicate that TNFRSF11A mutations contribute neither to the vast majority of cases of sporadic or familial PDB, nor to the development of osteosarcoma. More... »

PAGES

151-155

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s002230001211

DOI

http://dx.doi.org/10.1007/s002230001211

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042202761

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11351498


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