Investigation of IGF2, Hedgehog and fusion gene expression profiles in pediatric sarcomas

• Detection of fusion genes confirmed the histological diagnosis of pediatric sarcomas.
• PAX3/7–FOXO1 was present in 50% of ARMS, EWS–FLI1 in 60% of ES and SS18–SSX1/2 in 90% of SS samples.
• RMS showed a high expression of IGF2 while ES showed a low expression of IGF2 gene.
• ES showed high expression of Hedgehog genes.
• Hedgehog and IGF pathways may have a role in the development of pediatric sarcomas.

The childhood sarcomas are malignant tumors with high mortality rates. They are divided into two genetic categories: a category without distinct pattern karyotypic changes and the other category showing unique translocations that originate gene rearrangements. This category includes rhabdomyosarcoma (RMS), Ewing's sarcoma (ES) and synovial sarcoma (SS). Diverse studies have related development genes, such as; IGF2, IHH, PTCH1 and GLI1 and sarcomatogenesis.ObjectiveTo characterize the RMS, ES and SS rearrangements, we quantify the expression of IGF2 IHH, PTCH1 and GLI1 genes and correlate molecular data with clinical parameters of patients.DesignWe analyzed 29 RMS, 10 SS and 60 ES tumor samples by RT-PCR (polymerase chain reaction-reverse transcription) and qPCR (quantitative PCR).ResultsAmong the samples of ARMS, 50% had rearrangements of PAX3/7–FOXO1, 60% of ES samples were EWS–FLI1 positive and 90% of SS samples were positive for SS18–SSX1/2. In relation to the control reference samples (QPCR Human Reference Total RNA-Stratagene, Human Skeletal Muscle Total RNA-Ambion, Universal RNA Human Normal Tissues-Ambion), RMS samples showed a high IGF2 gene expression (p < 0.0001). Moreover, ES samples showed a low IGF2 gene expression (p < 0.0001) and high IHH (p < 0.0001), PTCH1 (p = 0.0173) and GLI1 (p = 0.0113) gene expressions.ConclusionsThe molecular characterization of IGF and Hedgehog pathway in these pediatric sarcomas may collaborate to enable a better understanding of the biological behavior of these neoplasms.