Green Darrell, Mohorianu Irina, Piec Isabelle, Turner Jeremy, Beadsmoore Clare, Toms Andoni, Ball Richard, Nolan John, McNamara Iain, Dalmay Tamas, Fraser William D
Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom.
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom.
Bone Rep. 2017 Sep 6;7:63-69. doi: 10.1016/j.bonr.2017.09.001. eCollection 2017 Dec.
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.
促排磷性间叶肿瘤是一组异质性的骨和软组织肿瘤，可引起多种副肿瘤综合征，如肿瘤诱发的骨软化症。“促排磷性”一词源于这些肿瘤分泌高水平成纤维细胞生长因子23这一常见发现，该因子会导致肾脏磷流失，进而引发低磷血症。促排磷性间叶肿瘤较为罕见，诊断困难。一名68岁、活动能力很强的男性患者出现骨痛和肌肉无力症状。他存在低磷血症，总碱性磷酸酶显著升高。患者开始补充维生素D，但病情仍进展。在出现症状的第五年，患者需要使用轮椅，并描述身体接触时有“爆炸性”骨痛。血清1,25-二羟维生素D水平较低，血清成纤维细胞生长因子23显著升高，这引发了对促排磷性间叶肿瘤的怀疑。在其左侧股骨头发现一处病变，患者接受了全髋关节置换术。患者病情迅速改善，在三年的随访期内恢复了积极的生活方式。由于分子检测可能有助于做出可靠诊断，尤其对罕见疾病很有用，我们采用了二代测序方法来鉴定切除肿瘤中小RNA的差异表达。小RNA是非编码RNA分子，在基因表达调控中起关键作用，可作为特异性生物标志物。我们发现miR-197上调。我们还发现miR-20b、miR-144和miR-335下调，这是骨肉瘤典型的小RNA谱。癌症中最常上调的微小RNA miR-21下调。我们得出结论，除致癌性miR-21下调外，特定的小RNA谱是骨肉瘤的典型特征。经计算预测靶向成纤维细胞生长因子23信使RNA的miR-197的转录可塑性，可能在细胞层面为纠正该蛋白的异位表达而上调。
