Gene expression profiles in fibroblast growth factor 23 (FGF23)-producing tumors provide new insights on diagnostic and therapeutic intervention.

Tumor-induced osteomalacia (TIO) is a rare disorder caused by phosphaturic mesenchymal tumor (PMT) that secrete fibroblast growth factor 23 (FGF23). There is limited data regarding the genetic of PMT. Fusion genes with FN1-FGFR1, FN1-FGF1, NIPBL-BEND2 have been reported , yet they are absent in 30-40% of PMTs. We conducted RNA sequencing on PMT and surrounding control tissue samples obtained during tumor resection in 5 patients, where PMTs were confirmed histologically. We identified 3261 differentially expressed (DE) genes between tumors and control tissues. Such DE genes were associated with musculoskeletal system diseases, mineralization, and pathways in cancer. We found de novo SNPs in regulatory regions of genes exhibiting statistically significant expression changes between control and PMT samples - ELOVL6, GM2A, NUDT4, that hold diagnostic and therapeutic relevance . We identified FN1-FGF1 fusion genes in 1 out of 5 PMT samples, confirming previous studies. We found that PMT overexpressed genes associated with osteoblast activity and differentiation, such as OPG/RANKL, highlighting tumor development. Healthy and PMT tissue samples from six patients.