7582 Genetic Profiling of Phosphaturic Mesenchymal Tumors Unravels Osterix's Significance in Tumor-Induced Osteomalacia

Abstract Disclosure: Y. Imanishi: None. Y. Nagata: None. M. Ohara: None. T. Maeda-Tateishi: None. T. Shoji: None. M. Emoto: None. Background & Purpose: Tumor-induced osteomalacia (TIO) is a rare condition caused by tumors releasing too much fibroblast growth factor 23 (FGF23). These tumors, specifically called phosphaturic mesenchymal tumors, mixed connective tissue variant (PMTMCT), lead to osteomalacia due to low serum phosphate levels. However, a detailed study regarding the genetic makeup of these tumors and their similarity to bone cells (osteoblasts/osteocytes) has been lacking. Methods: Nineteen PMTMCTs were analyzed and compared their gene expressions to 6 non-TIO tumors. Our focus was on genes usually found in bone cells. Additionally, we examined the relationship between FGF23 and these genes in PMTMCTs. One gene, Osterix, showing significant correlation was further studied using UMR106 osteoblast cells. Results: Fourteen genes related to bone cells expressed significantly higher in PMTMCTs compared to non-TIO tumors. Immunoblotting and Immunohistochemical examinations confirmed the presence of FGF23, Runx2, and Osterix in PMTMCTs. Particularly, Osterix showed the strongest link with FGF23 in PMTMCTs. Immunohistochemical tests revealed similar patterns of distribution for Osterix and FGF23, even co-localizing in some instances. However, the distribution of another gene, DMP1, differed from that of FGF23. In UMR106 cells, silencing Osterix expression led to decreased FGF23 expression, irrespective of DMP1 levels. Conclusions: PMTMCTs exhibit higher levels of genes associated with bone cell functions compared to other tumors. These tumors likely originated from mesenchymal stem cells and transformed into bone cells. Furthermore, Osterix might play a crucial role in the excessive release of FGF23 in PMTMCTs. Presentation: 6/1/2024