PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Alveolar rhabdomyosarcoma (ARMS) is driven by the PAX3-FOXO1 fusion protein.
• Fibroblast growth factor receptor 4 (FGFR4) is a known transcriptional target of PAX3-FOXO1.

Purpose of the Study:

• To investigate the role of FGFR4 as a potential effector of PAX3-FOXO1 in ARMS tumorigenesis.
• To determine if wild-type FGFR4 upregulation or activating FGFR4 mutations contribute to ARMS development.

Main Methods:

• Enhanced expression of wild-type FGFR4 in primary mouse myoblasts.
• Introduction of a constitutively active FGFR4 mutant into primary mouse myoblasts.
• Sequencing of FGFR4 mRNA from ARMS cell lines.

Main Results:

• Enhanced wild-type FGFR4 expression did not affect myoblast differentiation, proliferation, or transformation downstream of PAX3-FOXO1.
• A constitutively active FGFR4 mutant enhanced primary myoblast proliferation and transformation.
• No somatic mutations or single nucleotide polymorphisms in the FGFR4 coding region were found in ARMS cell lines.

Conclusions:

• Wild-type FGFR4 upregulation does not appear to contribute to PAX3-FOXO1-driven ARMS.
• Activating mutations in FGFR4 may play a role in ARMS development and progression.
• FGFR4 is not somatically mutated in ARMS cell lines.