2246

FGF1

AFGF|ECGF|ECGF-beta|ECGFA|ECGFB|FGF-alpha|FGFA|GLIO703|HBGF1;fibroblast growth factor 1 (acidic);FGF1;fibroblast growth factor 1 (acidic)

HBGF-1|acidic fibroblast growth factor|beta-endothelial cell growth factor|endothelial cell growth factor, alpha|endothelial cell growth factor, beta|heparin-binding growth factor 1

5q31

protein-coding

Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. Theyresemble developing skeletal muscle and are histologically divided into two mainsubtypes; alveolar and embryonal RMS. Characteristic genomic aberrations, including the PAX3- and PAX7-FOXO1 fusion genes in alveolar cases, have led to increased understanding of their molecular biology. Here, we determined the effect of genomic copy number on gene expression levels through array comparative genomic hybridization (CGH) analysis of 13 RMS cell lines, confirmed by multiplex ligation-dependent probe amplification copy number analyses, combined with theircorresponding expression profiles. Genes altered at the transcriptional level bygenomic imbalances were identified and the effect on expression was proportionalto the level of genomic imbalance. Extrapolating to a public expression profiling dataset for 132 primary RMS identified features common to the cell lines and primary samples and associations with subtypes and fusion gene status. Genes identified such as CDK4 and MYCN are known to be amplified, overexpressed, and involved in RMS tumorigenesis. Of the many genes identified, those with likely functional relevance included CENPF, DTL, MYC, EYA2, and FGFR1. Copy number and expression of FGFR1 was validated in additional primary material and found amplified in 6 out of 196 cases and overexpressed relative to skeletal muscle and myoblasts, with significantly higher expression levels in the embryonal comparedwith alveolar subtypes. This illustrates the ability to identify genes of potential significance in tumor development through combining genomic and transcriptomic profiles from representative cell lines with publicly available expression profiling data from primary tumors.