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2017 ; 7
(ä): 63-69
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MicroRNA expression in a phosphaturic mesenchymal tumour
#MMPMID28932769
Green D
; Mohorianu I
; Piec I
; Turner J
; Beadsmoore C
; Toms A
; Ball R
; Nolan J
; McNamara I
; Dalmay T
; Fraser WD
Bone Rep
2017[Dec]; 7
(ä): 63-69
PMID28932769
show ga
Phosphaturic mesenchymal tumours are a heterogeneous set of bone and soft tissue
neoplasms that can cause a number of paraneoplastic syndromes such as tumour
induced osteomalacia. The term phosphaturic comes from the common finding that
these tumours secrete high levels of fibroblast growth factor 23 which causes
renal phosphate wasting leading to hypophosphatemia. Phosphaturic mesenchymal
tumours are rare and diagnosis is difficult. A very active 68 year old male
presented with bone pain and muscle weakness. He was hypophosphataemic and total
alkaline phosphatase was markedly elevated. The patient was placed on vitamin D
supplementation but his condition progressed. In the fifth year of presentation
the patient required the use of a wheelchair and described "explosive" bone pain
on physical contact. Serum 1,25 dihydroxyvitamin D was low and serum fibroblast
growth factor 23 was significantly elevated, raising suspicion of a phosphaturic
mesenchymal tumour. A lesion was detected in his left femoral head and the
patient underwent a total hip replacement. The patient displayed a rapid
improvement to his condition and during a three year follow up period he returned
to an active lifestyle. As molecular testing may help provide a robust diagnosis
and is particularly useful in rare diseases we took a next generation sequencing
approach to identify a differential expression of small RNAs in the resected
tumour. Small RNAs are non-coding RNA molecules that play a key role in
regulation of gene expression and can be used as specific biomarkers. We found an
upregulation of miR-197. We also found a downregulation of miR-20b, miR-144 and
miR-335 which is a small RNA profile typical of osteosarcoma. MiR-21, the most
frequently upregulated microRNA in cancer, was downregulated. We conclude that
the specific small RNA profile is typical of osteosarcoma except for the
downregulation of oncogenic miR-21. Transcriptional plasticity of miR-197, which
is computationally predicted to target fibroblast growth factor 23 messenger RNA,
may be upregulated in a cellular effort to correct the ectopic expression of the
protein.
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