PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma
Article first published online: 31 AUG 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 51, Issue 10, pages 807–815, October 2012
How to Cite
Marshall, A. D., van der Ent, M. A. and Grosveld, G. C. (2012), PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma. Mol. Carcinog., 51: 807–815. doi: 10.1002/mc.20848
- Issue published online: 11 SEP 2012
- Article first published online: 31 AUG 2011
- Manuscript Accepted: 27 JUL 2011
- Manuscript Revised: 16 JUN 2011
- Manuscript Received: 13 DEC 2010
- alveolar rhabdomyosarcoma
We and others have identified FGFR4 as a direct transcriptional target of the alveolar rhabdomyosarcoma (ARMS) specific fusion protein, PAX3-FOXO1. We hypothesized fibroblast growth factor receptor 4 (FGFR4) may act as an effector of PAX3-FOXO1, contributing to PAX3-FOXO1 tumorigenic phenotypes. However, we demonstrate that enhanced expression of FGFR4 does not contribute to inhibited differentiation, enhanced proliferation, or transformation downstream of PAX3-FOXO1 in primary mouse myoblasts. Therefore we were unable to identify any contribution of up regulation of wild type FGFR4 to PAX3-FOXO1 driven tumorigenesis. Conversely, a constitutively active mutant of FGFR4 can enhance primary myoblast proliferation and transformation, indicating activating mutations of FGFR4 could contribute to the development and progression of ARMS. We sequenced the FGFR4 mRNA from five ARMS cell lines and identified no somatic mutations, nor any association with any human single nucleotide polymorphism within the FGFR4 coding region. © 2011 Wiley Periodicals, Inc.