IndraLab
Statements
sparser
"For example, an FN1‐FGFR1 fusion gene has been identified in several TIO tumors; this gene has been hypothesized to cause tumorigenesis in TIO through FGF23 binding, leading to autocrine or paracrine activation of the receptor tyrosine kinase. ( xref , xref ) Interestingly, FGFR1 fusion genes have been identified as pathogenic in the 8p11 myeloproliferative syndrome, breast cancer, glioblastoma, and lung squamous cell carcinoma. ( xref , xref ) Additionally, similar microRNA profiles were recently noted in osteosarcomas and TIO; both show upregulation of the biomarker miR‐197 and downregulation of miR‐20b, miR‐144, and miR‐335. ( xref ) Further genetic studies of TIO may improve our understanding of the disease and identify patients missed by currently available modalities."
sparser
"A relevant finding in the study of PMT pathogenesis identified FN1 and FGFR1 translocations as a leading cause of FN1‐FGFR1 fusion protein in 60% of samples by RNA sequencing or fluorescence in situ hybridization (FISH). xref The FN1‐FGFR1 fusion gene would presumably be highly expressed since FN1 is an ubiquitously expressed extracellular protein and is driven by a strong promoter. xref In this way, FGF23 secretion would be up‐regulated to down‐regulate the levels of phosphate and other biomolecules associated with PMTs."
sparser
"TIO is caused by mesenchymal tumours often described as hemangioperitomas, which secrete FGF23 and cause a paraneoplastic renal phosphate wasting syndrome with osteomalacia and muscle weakness. ( xref ) RNA-seq analysis of FGF23-producing tumours revealed fibronectin (FN)- FGF1 or FN-FGFR1 gene rearrangements, which may activate FGFR1 in an autocrine fashion that stimulates FGF23 production by these tumours. ( xref ) Increased KL expression may constitute a second positive feedback loop to increase FGF23 production in TIO tumours, suggesting that the autocrine stimulation of FGF23 and the manifestations of TIO may be KL-dependent, however this requires further study. ( xref )"
sparser
"A relevant finding in understanding its tumorigenesis was the identification of fibronectin 1 ( FN1 ) and fibroblast growth factor receptor‐1 ( FGFR1 ) translocations which led to an FN1‐FGFR1 fusion protein in 60% of studied PMTs by RNA sequencing or FGFR‐specific fluorescence in situ hybridization (FISH). xref Additional studies have confirmed this finding in a larger group of PMTs. xref In addition to the description of the FN1‐FGFR1 translocation, it has been recently reported that 6% of PMTs had an FN1 ‐fibroblast growth factor 1 ( FGF1 ) translocation. xref However, these findings still suggest the existence of the tumorigenic drivers behind the fusion‐negative cases, and the mutational landscape and genetic signatures of PMTs are yet to be elucidated."
sparser
"Reduced serum 1,25(OH) 2 D and elevated bone‐specific alkaline phosphatase can be used as diagnostic markers, and if measured, serum FGF23 is typically elevated. xref In a large TIO series, 48% of tumors exhibited evidence for translocations resulting in abnormal fusion proteins of fibronectin 1 (FN1) and either fibroblast growth factor receptor 1 (FGFR1) or fibroblast growth factor 1 (FGF1) (3/50 [6%] FN1‐FGFR1 and 21/50 [42%] FN1‐FGF1), hypothesized to generate an autocrine function loop. xref Complete removal of the tumor by wide resection or ablation is typically curative of the biochemical abnormalities with improvement in bone and muscle strength. xref However, these mesenchymal tumors are slow growing and may be difficult to localize."
sparser
"While the currently described patient is PTEN mutation-negative, high levels of phosphorylated AKT and phosphorylated S6 were detected on immunohistochemical staining (data not shown), supporting the concept that the AKT pathway is activated in tumor cells, perhaps due to translocation-mediated signaling through the chimeric FN1-FGFR1 receptor."
sparser
"Specifically, fusion of fibronectin 1 (FN1) with FGFR1 or FGF1 creates aberrant fusion genes FN1-FGFR1 and FN1-FGF1, which are overexpressed in 42% and 6% of PMT, respectively [ xref ], while aberrant α -Klotho (or less commonly β -Klotho) genes are overexpressed in 8 of 10 fusion-negative PMT [ xref ]."