Identification of a novel FN1–FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour

  title={Identification of a novel FN1–FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour},
  author={Jen-Chieh Lee and Yung‐Ming Jeng and Sheng-Yao Su and Chen‐Tu Wu and K. -S. Tsai and Cheng-Han Lee and Chung-Yen Lin and Jodi M. Carter and Jenq-Wen Huang and Shu-Hwa Chen and Shyang-Rong Shih and Adrian Mari{\~n}o-Enr{\'i}quez and Chih-Chi Chen and Andrew L. Folpe and Yih-Leong Chang and Cher‐Wei Liang},
  journal={The Journal of Pathology},
Phosphaturic mesenchymal tumours (PMTs) are uncommon soft tissue and bone tumours that typically cause hypophosphataemia and tumour‐induced osteomalacia (TIO) through secretion of phosphatonins including fibroblast growth factor 23 (FGF23). PMT has recently been accepted by the World Health Organization as a formal tumour entity. The genetic basis and oncogenic pathways underlying its tumourigenesis remain obscure. In this study, we identified a novel FN1–FGFR1 fusion gene in three out of four… 

Characterization of FN1–FGFR1 and novel FN1–FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors

Insight is provided into possible mechanisms underlying the pathogenesis of phosphaturic mesenchymal tumor and imply a central role of the FGF1-FGFR1 signaling pathway.

Frequent overexpression of klotho in fusion-negative phosphaturic mesenchymal tumors with tumorigenic implications

The results demonstrated the utility of AMP-seq, which was compromised by decalcification and prolonged archiving, and identified FN1-FGFR1/FGF1 fusion genes in nearly half of PMT, suggesting a central role of FGFR1 pathways in the pathogenesis ofPMT.

Fibroblast growth factor receptor 1 (FGFR1) expression in phosphaturic mesenchymal tumors.

  • S. TajimaM. Fukayama
  • Medicine, Biology
    International journal of clinical and experimental pathology
  • 2015
Analysis of phosphaturic mesenchymal tumor cases found that 36% of cases exhibited cytoplasmic and membranous staining with strong intensity, and FGF23 serum level does not correlate with FGFR1 membranOUS expression (staining withStrong intensity), leading to speculation that important factors other thanFGFR1 are involved in the tumor biology of PMTs overexpressing FGF 23.

Calcified chondroid mesenchymal neoplasms with FN1-receptor tyrosine kinase gene fusions including FGFR2, FGFR1, MERTK, NTRK1, and TEK: a molecular and clinicopathologic analysis

Translocations involving FN1 have been described in a variety of neoplasms that share the presence of a cartilage matrix and may also contain a variable extent of calcification. Fusions of FN1 to

Calcified chondroid mesenchymal neoplasms with FN1-receptor tyrosine kinase gene fusions including MERTK, TEK, FGFR2, and FGFR1: a molecular and clinicopathologic analysis

Novel findings are described that expand the morphologic spectrum of these neoplasms and have been labeled as calcified chondroid mesenchymal neoplasm, showing a predilection for the TMJ region and the extremities.

The novel finding of an FGFR1::TACC1 fusion in an undifferentiated spindle cell sarcoma of soft tissue with aggressive clinical course

The finding of FGFR1‐TACC1 fusion in a high‐grade, undifferentiated spindle cell sarcoma of soft tissue is novel and may offer a potential therapeutic target in the near future.

Immunohistochemical and molecular detection of the expression of FGF23 in phosphaturic mesenchymal tumors including the non-phosphaturic variant

In conclusion, immunohistochemistry for FGF23 is an useful diagnostic adjunct for PMT, although its utility appears to be limited in cases without TIO.

Phosphaturic Mesenchymal Tumors: Clinicopathologic, Immunohistochemical and Molecular Analysis of 22 Cases Expanding their Morphologic and Immunophenotypic Spectrum

The unifying immunophenotype of the neoplastic cells irrespective of the histologic pattern suggests a specific disease entity with diverse morphotypes/variants rather than different neoplasms unified by TIO.

FN1–EGF gene fusions are recurrent in calcifying aponeurotic fibroma

The FN1–EGF fusion, which has not been observed in any other neoplasm, appears to be the main driver mutation in CAF, and the composition of the chimera suggests an autocrine/paracrine mechanism of transformation.

Clinicopathologic and molecular features of six cases of phosphaturic mesenchymal tumor

It is suggested that IHC and molecular analysis can aid in the diagnosis of phosphaturic mesenchymal tumors, guiding excision of the tumor and resolution of osteomalacia.



A Novel Chromogenic In Situ Hybridization Assay for FGF23 mRNA in Phosphaturic Mesenchymal Tumors

RNAscope is a highly sensitive and specific, semiquantitative in situ hybridization method of FGF23 mRNA detection applicable to formalin-fixed, paraffin-embedded tissues and reduces “false positives” related to detection of endogenous F GF23 mRNA expression by osteocytes.

Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation.

It is demonstrated here that OD is caused by missense mutations in highly conserved residues comprising the ligand-binding and transmembrane domains of FGFR1, thus defining novel roles for this receptor as a negative regulator of long-bone growth.

Most Osteomalacia-associated Mesenchymal Tumors Are a Single Histopathologic Entity: An Analysis of 32 Cases and a Comprehensive Review of the Literature

Most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT, and improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other meschymal tumors.

Emergence of FGFR family gene fusions as therapeutic targets in a wide spectrum of solid tumours

The ability to exploit the unique targetability of FGFR fusions proves that FGFR‐derived therapies could have a promising future in cancer therapeutics, and understanding the diverse mechanisms ofFGFR fusion formation and their oncogenic potential will shed light on the impact of FG FR‐derived therapy in the future.

Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia

It is concluded that overproduction of F GF23 causes TIO, whereas mutations in the FGF23 gene result in autosomal dominant hypophosphatemic rickets possibly by preventing proteolytic cleavage and enhancing biological activity of FGF 23.

Chimeric EWS-FLI1 transcript in a Ewing cell line with a complex t(11;22;14) translocation.

Direct sequencing was performed to demonstrate that the molecular rearrangement in this particular Ewing sample resulted in a fusion transcript similar to those observed in tumors with the prototypical translocation.

Identification of fusion genes in breast cancer by paired-end RNA-sequencing

RNA interference-mediated knock-down of the VAPB-IKZF3 fusion gene indicated that it may be necessary for cancer cell growth and survival, and a number of novel fusion genes in breast cancer cells are discovered using RNA-sequencing and improved bioinformatic stratification.

Identification of anaplastic lymphoma kinase as a potential therapeutic target in ovarian cancer.

It is shown that the anaplastic lymphoma kinase (ALK) is aberrantly activated in ovarian cancer and ALK is identified as a potential therapeutic target in a subset of serous ovarian carcinoma and stromal sarcoma patients.

Anti-fibroblast growth factor 23 antibody therapy

  • S. Fukumoto
  • Biology, Medicine
    Current opinion in nephrology and hypertension
  • 2014
These recent findings confirm that FGF23 has a pivotal role in phosphate metabolism, and the inhibition of FGF 23 production or activity is promising as a new therapy for F GF23-related hypophosphatemic diseases.