Mutation screening of the TNFRSF11A gene encoding receptor activator of NF kappa B (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma

A. B. Sparks, S. N. Peterson, B. J. Lofthus, Lynne Hocking, D. P. Cahill, F. J. Frassica, E. A. Streeten, M. A. Levine, C. M. Fraser, M. D. Adams

Research output: Contribution to journalArticle

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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 kappaB (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 Pager's disease including several individuals with early onset Pager'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.

Original languageEnglish
Pages (from-to)151-155
Number of pages4
JournalCalcified Tissue International
Volume68
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • Paget's disease
  • osteosarcoma
  • DNA
  • genetic
  • TNFRSF11A
  • osteoclast differentiation factor
  • chromosome 18Q
  • expansile oseolysis
  • colorectal-cancer
  • linkage
  • ligand
  • aggregation
  • frequency
  • cytokine

Cite this

Mutation screening of the TNFRSF11A gene encoding receptor activator of NF kappa B (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma. / Sparks, A. B.; Peterson, S. N.; Lofthus, B. J.; Hocking, Lynne; Cahill, D. P.; Frassica, F. J.; Streeten, E. A.; Levine, M. A.; Fraser, C. M.; Adams, M. D.

In: Calcified Tissue International, Vol. 68, No. 3, 2001, p. 151-155.

Research output: Contribution to journalArticle

Sparks, AB, Peterson, SN, Lofthus, BJ, Hocking, L, Cahill, DP, Frassica, FJ, Streeten, EA, Levine, MA, Fraser, CM & Adams, MD 2001, 'Mutation screening of the TNFRSF11A gene encoding receptor activator of NF kappa B (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma' Calcified Tissue International, vol. 68, no. 3, pp. 151-155. https://doi.org/10.1007/s002230001211
Sparks, A. B. ; Peterson, S. N. ; Lofthus, B. J. ; Hocking, Lynne ; Cahill, D. P. ; Frassica, F. J. ; Streeten, E. A. ; Levine, M. A. ; Fraser, C. M. ; Adams, M. D. / Mutation screening of the TNFRSF11A gene encoding receptor activator of NF kappa B (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma. In: Calcified Tissue International. 2001 ; Vol. 68, No. 3. pp. 151-155.
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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 kappaB (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 Pager's disease including several individuals with early onset Pager'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.",
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T1 - Mutation screening of the TNFRSF11A gene encoding receptor activator of NF kappa B (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma

AU - Sparks, A. B.

AU - Peterson, S. N.

AU - Lofthus, B. J.

AU - Hocking, Lynne

AU - Cahill, D. P.

AU - Frassica, F. J.

AU - Streeten, E. A.

AU - Levine, M. A.

AU - Fraser, C. M.

AU - Adams, M. D.

PY - 2001

Y1 - 2001

N2 - 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 kappaB (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 Pager's disease including several individuals with early onset Pager'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.

AB - 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 kappaB (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 Pager's disease including several individuals with early onset Pager'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.

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KW - osteosarcoma

KW - DNA

KW - genetic

KW - TNFRSF11A

KW - osteoclast differentiation factor

KW - chromosome 18Q

KW - expansile oseolysis

KW - colorectal-cancer

KW - linkage

KW - ligand

KW - aggregation

KW - frequency

KW - cytokine

U2 - 10.1007/s002230001211

DO - 10.1007/s002230001211

M3 - Article

VL - 68

SP - 151

EP - 155

JO - Calcified Tissue International

JF - Calcified Tissue International

SN - 0171-967X

IS - 3

ER -