Tumor-induced osteomalacia in association with PTEN-negative Cowden syndrome

J. A. Berglund, R. I. Gafni, F. Wodajo, E. W. Cowen, Diala El-Maouche, R. Chang, C. C. Chen, L. C. Guthrie, A. A. Molinolo, M. T. Collins

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic condition in which phosphaturic mesenchymal tumors (PMTs) secrete high levels of fibroblast growth factor 23 (FGF23) into the circulation. This results in renal phosphate wasting, hypophosphatemia, muscle weakness, bone pain, and pathological fractures. Recent studies suggest that fibronectin-fibroblast growth factor receptor 1 (FN1-FGFR1) translocations may be a driver of tumorigenesis. We present a patient with TIO who also exhibited clinical findings suggestive of Cowden syndrome (CS), a rare autosomal dominant disorder characterized by numerous benign hamartomas, as well as an increased risk for multiple malignancies, such as thyroid cancer. While CS is a clinical diagnosis, most, but not all, harbor a mutation in the tumor suppressor gene PTEN. Genetic testing revealed a somatic FN1-FGFR1 translocation in the FGF23-producing tumor causing TIO; however, a germline PTEN mutation was not identified. To our knowledge, this is the first reported case of concurrent TIO and CS.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalOsteoporosis International
DOIs
StateAccepted/In press - Jan 29 2018
Externally publishedYes

Fingerprint

Multiple Hamartoma Syndrome
Receptor, Fibroblast Growth Factor, Type 1
Hypophosphatemia
Neoplasms
Spontaneous Fractures
Hamartoma
Germ-Line Mutation
Bone Fractures
Muscle Weakness
Genetic Testing
Tumor Suppressor Genes
Thyroid Neoplasms
Fibronectins
Carcinogenesis
Phosphates
Kidney
Pain
Mutation
Oncogenic osteomalacia

Keywords

  • Cowden syndrome
  • FGF23
  • FN1-FGFR1
  • Phosphaturic mesenchymal tumor
  • PTEN
  • Tumor-induced osteomalacia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Berglund, J. A., Gafni, R. I., Wodajo, F., Cowen, E. W., El-Maouche, D., Chang, R., ... Collins, M. T. (Accepted/In press). Tumor-induced osteomalacia in association with PTEN-negative Cowden syndrome. Osteoporosis International, 1-5. https://doi.org/10.1007/s00198-017-4372-x

Tumor-induced osteomalacia in association with PTEN-negative Cowden syndrome. / Berglund, J. A.; Gafni, R. I.; Wodajo, F.; Cowen, E. W.; El-Maouche, Diala; Chang, R.; Chen, C. C.; Guthrie, L. C.; Molinolo, A. A.; Collins, M. T.

In: Osteoporosis International, 29.01.2018, p. 1-5.

Research output: Contribution to journalArticle

Berglund, JA, Gafni, RI, Wodajo, F, Cowen, EW, El-Maouche, D, Chang, R, Chen, CC, Guthrie, LC, Molinolo, AA & Collins, MT 2018, 'Tumor-induced osteomalacia in association with PTEN-negative Cowden syndrome', Osteoporosis International, pp. 1-5. https://doi.org/10.1007/s00198-017-4372-x
Berglund, J. A. ; Gafni, R. I. ; Wodajo, F. ; Cowen, E. W. ; El-Maouche, Diala ; Chang, R. ; Chen, C. C. ; Guthrie, L. C. ; Molinolo, A. A. ; Collins, M. T. / Tumor-induced osteomalacia in association with PTEN-negative Cowden syndrome. In: Osteoporosis International. 2018 ; pp. 1-5.
@article{6c73a9ae98ca4496a8e7ae6a8b7cdeae,
title = "Tumor-induced osteomalacia in association with PTEN-negative Cowden syndrome",
abstract = "Tumor-induced osteomalacia (TIO) is a rare paraneoplastic condition in which phosphaturic mesenchymal tumors (PMTs) secrete high levels of fibroblast growth factor 23 (FGF23) into the circulation. This results in renal phosphate wasting, hypophosphatemia, muscle weakness, bone pain, and pathological fractures. Recent studies suggest that fibronectin-fibroblast growth factor receptor 1 (FN1-FGFR1) translocations may be a driver of tumorigenesis. We present a patient with TIO who also exhibited clinical findings suggestive of Cowden syndrome (CS), a rare autosomal dominant disorder characterized by numerous benign hamartomas, as well as an increased risk for multiple malignancies, such as thyroid cancer. While CS is a clinical diagnosis, most, but not all, harbor a mutation in the tumor suppressor gene PTEN. Genetic testing revealed a somatic FN1-FGFR1 translocation in the FGF23-producing tumor causing TIO; however, a germline PTEN mutation was not identified. To our knowledge, this is the first reported case of concurrent TIO and CS.",
keywords = "Cowden syndrome, FGF23, FN1-FGFR1, Phosphaturic mesenchymal tumor, PTEN, Tumor-induced osteomalacia",
author = "Berglund, {J. A.} and Gafni, {R. I.} and F. Wodajo and Cowen, {E. W.} and Diala El-Maouche and R. Chang and Chen, {C. C.} and Guthrie, {L. C.} and Molinolo, {A. A.} and Collins, {M. T.}",
year = "2018",
month = "1",
day = "29",
doi = "10.1007/s00198-017-4372-x",
language = "English (US)",
pages = "1--5",
journal = "Osteoporosis International",
issn = "0937-941X",
publisher = "Springer London",

}

TY - JOUR

T1 - Tumor-induced osteomalacia in association with PTEN-negative Cowden syndrome

AU - Berglund, J. A.

AU - Gafni, R. I.

AU - Wodajo, F.

AU - Cowen, E. W.

AU - El-Maouche, Diala

AU - Chang, R.

AU - Chen, C. C.

AU - Guthrie, L. C.

AU - Molinolo, A. A.

AU - Collins, M. T.

PY - 2018/1/29

Y1 - 2018/1/29

N2 - Tumor-induced osteomalacia (TIO) is a rare paraneoplastic condition in which phosphaturic mesenchymal tumors (PMTs) secrete high levels of fibroblast growth factor 23 (FGF23) into the circulation. This results in renal phosphate wasting, hypophosphatemia, muscle weakness, bone pain, and pathological fractures. Recent studies suggest that fibronectin-fibroblast growth factor receptor 1 (FN1-FGFR1) translocations may be a driver of tumorigenesis. We present a patient with TIO who also exhibited clinical findings suggestive of Cowden syndrome (CS), a rare autosomal dominant disorder characterized by numerous benign hamartomas, as well as an increased risk for multiple malignancies, such as thyroid cancer. While CS is a clinical diagnosis, most, but not all, harbor a mutation in the tumor suppressor gene PTEN. Genetic testing revealed a somatic FN1-FGFR1 translocation in the FGF23-producing tumor causing TIO; however, a germline PTEN mutation was not identified. To our knowledge, this is the first reported case of concurrent TIO and CS.

AB - Tumor-induced osteomalacia (TIO) is a rare paraneoplastic condition in which phosphaturic mesenchymal tumors (PMTs) secrete high levels of fibroblast growth factor 23 (FGF23) into the circulation. This results in renal phosphate wasting, hypophosphatemia, muscle weakness, bone pain, and pathological fractures. Recent studies suggest that fibronectin-fibroblast growth factor receptor 1 (FN1-FGFR1) translocations may be a driver of tumorigenesis. We present a patient with TIO who also exhibited clinical findings suggestive of Cowden syndrome (CS), a rare autosomal dominant disorder characterized by numerous benign hamartomas, as well as an increased risk for multiple malignancies, such as thyroid cancer. While CS is a clinical diagnosis, most, but not all, harbor a mutation in the tumor suppressor gene PTEN. Genetic testing revealed a somatic FN1-FGFR1 translocation in the FGF23-producing tumor causing TIO; however, a germline PTEN mutation was not identified. To our knowledge, this is the first reported case of concurrent TIO and CS.

KW - Cowden syndrome

KW - FGF23

KW - FN1-FGFR1

KW - Phosphaturic mesenchymal tumor

KW - PTEN

KW - Tumor-induced osteomalacia

UR - http://www.scopus.com/inward/record.url?scp=85041115133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041115133&partnerID=8YFLogxK

U2 - 10.1007/s00198-017-4372-x

DO - 10.1007/s00198-017-4372-x

M3 - Article

SP - 1

EP - 5

JO - Osteoporosis International

JF - Osteoporosis International

SN - 0937-941X

ER -