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

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, Kenneth W Kinzler, Bert Vogelstein, S. H. Ralston

Research output: Contribution to journalArticle

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 NFκB (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.

Original languageEnglish (US)
Pages (from-to)151-155
Number of pages5
JournalCalcified Tissue International
Volume68
Issue number3
DOIs
StatePublished - 2001

Fingerprint

Osteosarcoma
Mutation
Genes
Osteitis Deformans
Bone and Bones
DNA
Developmental Bone Disease
Familial Paget's disease of bone
Chromosomes, Human, Pair 22
Cell Line
Spontaneous Fractures
Insertional Mutagenesis
Loss of Heterozygosity
Bone Resorption
Pain

Keywords

  • DNA
  • Genetic
  • Osteosarcoma
  • Paget's disease
  • TNFRSF11A

ASJC Scopus subject areas

  • Endocrinology

Cite this

Mutation screening of the TNFRSF11A gene encoding receptor activator of NFκB (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma. / Sparks, A. B.; Peterson, S. N.; Bell, C.; Loftus, B. J.; Hocking, L.; Cahill, D. P.; Frassica, F. J.; Streeten, E. A.; Levine, M. A.; Fraser, C. M.; Adams, M. D.; Broder, S.; Venter, J. C.; Kinzler, Kenneth W; Vogelstein, Bert; Ralston, S. H.

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

Research output: Contribution to journalArticle

Sparks, AB, Peterson, SN, Bell, C, Loftus, BJ, Hocking, L, Cahill, DP, Frassica, FJ, Streeten, EA, Levine, MA, Fraser, CM, Adams, MD, Broder, S, Venter, JC, Kinzler, KW, Vogelstein, B & Ralston, SH 2001, 'Mutation screening of the TNFRSF11A gene encoding receptor activator of NFκB (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. ; Bell, C. ; Loftus, B. J. ; Hocking, L. ; Cahill, D. P. ; Frassica, F. J. ; Streeten, E. A. ; Levine, M. A. ; Fraser, C. M. ; Adams, M. D. ; Broder, S. ; Venter, J. C. ; Kinzler, Kenneth W ; Vogelstein, Bert ; Ralston, S. H. / Mutation screening of the TNFRSF11A gene encoding receptor activator of NFκB (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma. In: Calcified Tissue International. 2001 ; Vol. 68, No. 3. pp. 151-155.
@article{a216e35f24e14f73973eb55c87a68aa2,
title = "Mutation screening of the TNFRSF11A gene encoding receptor activator of NFκB (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma",
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 NFκB (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.",
keywords = "DNA, Genetic, Osteosarcoma, Paget's disease, TNFRSF11A",
author = "Sparks, {A. B.} and Peterson, {S. N.} and C. Bell and Loftus, {B. J.} and L. Hocking and Cahill, {D. P.} and Frassica, {F. J.} and Streeten, {E. A.} and Levine, {M. A.} and Fraser, {C. M.} and Adams, {M. D.} and S. Broder and Venter, {J. C.} and Kinzler, {Kenneth W} and Bert Vogelstein and Ralston, {S. H.}",
year = "2001",
doi = "10.1007/s002230001211",
language = "English (US)",
volume = "68",
pages = "151--155",
journal = "Calcified Tissue International",
issn = "0171-967X",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - Mutation screening of the TNFRSF11A gene encoding receptor activator of NFκB (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma

AU - Sparks, A. B.

AU - Peterson, S. N.

AU - Bell, C.

AU - Loftus, B. J.

AU - Hocking, L.

AU - Cahill, D. P.

AU - Frassica, F. J.

AU - Streeten, E. A.

AU - Levine, M. A.

AU - Fraser, C. M.

AU - Adams, M. D.

AU - Broder, S.

AU - Venter, J. C.

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

AU - Ralston, S. H.

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 NFκB (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.

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 NFκB (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.

KW - DNA

KW - Genetic

KW - Osteosarcoma

KW - Paget's disease

KW - TNFRSF11A

UR - http://www.scopus.com/inward/record.url?scp=17744368015&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17744368015&partnerID=8YFLogxK

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 -