磷酸盐尿性间叶瘤（PMT）致低磷性骨软化症虽然属于临床少见病，但由于早期确诊非常难，容易误诊，致残率高，已证实血FGF23水平过高是发病的关键因素，一旦切除瘤组织血磷恢复正常，骨软化症状改善乃至痊愈。已有研究发现瘤组织存在2个融合基因，可能是导致瘤组织自分泌或旁分析分泌FGF23的分子遗传机制，但仅能解释少部分PMT患者，因此确切的分子遗传机制尚待阐明。本课题拟在我们已建立的53例PMT致低磷性软化症患者切除瘤组织样本库，以及前期二代测序获得瘤组织体细胞突变基础上，继续收集上述患者组织样本等40例，达到93例，对外周血及切除瘤组织基因组DNA行全外显子组测序等，试图鉴定体细胞致病基因突变及其功能，以及瘤组织RNA行转录组测序和荧光原位杂交等，以鉴定新的融合基因。本项目不仅为肿瘤性低磷骨软化症发病的确切分子遗传机制提供重要数据，而且有助于发现新的分子靶向检查手段，以提高该疑难病的早期确诊率。

Although hypophosphatemic osteomalacia caused by phosphate urinary mesenchymal tumors (PMT) is a rare disease in clinic, early diagnosis is very difficult, easy to misdiagnose and high disability rate. It has been proved that the high level of serum fibroblast growth factor 23 is the key factor in the pathogenesis of PMT. Once the blood phosphorus of resected tumors returns to normal, the symptoms of osteomalacia will improve and even recover. It has been found that there are two fusion genes in tumor tissue, which may be the molecular genetic mechanism of autocrine or paracrine secretion of fibroblast growth factor 23. However, only a few PMT patients can be explained, so the exact molecular genetic mechanism remains to be elucidated. In this study, we will continue to collect 40 samples of PMT-induced hypophosphoric osteomalacia from 53 patients who have resected the tumor tissue sample bank and obtained somatic cell mutations by second-generation sequencing, reaching 93 cases. We will try to identify somatic cell pathogenic gene mutations and their functions by next-generation sequencing the genomic DNA of peripheral blood and resected tumors. In order to identify new fusion genes, RNA transcriptome sequencing and fluorescence in situ hybridization will be performed. This project not only provides important data for the exact molecular genetic mechanism of tumor induced hypophosphatemic osteomalacia, but also helps to find new molecular targeting methods to improve the early diagnosis rate of this difficult disease.