Expression of ligand-activated KIT and platelet-derived growth factor receptor beta tyrosine kinase receptors in

Elena Tamborini1, Lorena Bonadiman, Angela Greco

  • 1Experimental Molecular Pathology, Department of Pathology and Departments of Experimental Oncology, Istituto Nazionale per lo Studio e al Cura dei Tumori, via G. Venezian, 1, 20133 Milan, Italy.

Abstract

Insights

Activated KIT and PDGFRbeta receptors are present in about 70% of Synovial Sarcoma (SS) cases, suggesting potential therapeutic targets. These findings highlight the role of tyrosine kinase inhibitors in treating SS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tyrosine kinase receptor inhibitors offer a promising therapeutic avenue for tumors with activated receptors.
  • Previous research indicated KIT and stem cell factor (SCF) mRNA coexpression in Synovial Sarcomas (SS), with some cases showing activated receptors.
  • This study expands on prior findings by investigating KIT and platelet-derived growth factor receptor beta (PDGFRbeta) expression and activation in a larger cohort of SS cases.

Purpose of the Study:

  • To investigate the expression levels and phosphorylation status of KIT and PDGFRbeta in Synovial Sarcomas.
  • To evaluate the potential of KIT and PDGFRbeta as therapeutic targets for tyrosine kinase inhibitor therapy in SS.
  • To explore the relationship between receptor activation and their cognate ligands in SS.

Main Methods:

  • Analysis of 43 SS cases for KIT and PDGFRbeta expression and activation using immunoprecipitation and Western blotting.
  • Detection of SCF and PDGFB ligands via reverse transcription-polymerase chain reaction (RT-PCR).

Main Results:

  • KIT was expressed in 45% and PDGFRbeta in 45% of SS cases (monophasic and biphasic combined).
  • Receptors were phosphorylated when expressed, and their ligands were detected in all activated cases.
  • Expression patterns varied between SS subtypes and fusion transcript types (SYTSSX1/SYTSSX2).

Conclusions:

  • Approximately 70% of SS cases express at least one activated tyrosine kinase receptor (KIT or PDGFRbeta), often with mutually exclusive expression.
  • Coexpression of KIT and PDGFRbeta is infrequent and primarily observed in the monophasic subtype.
  • These findings suggest that a significant proportion of SS patients could benefit from targeted therapies acting on KIT and PDGFRbeta, potentially driven by autocrine signaling loops.

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