SS is a high grade malignant
SS is a high-grade malignant soft tissue sarcoma accounting for 5%–10% of soft tissue sarcomas. After RMS, SS is the most common sarcoma in children, adolescents and young adults . SS originates primarily in the lower (62%) and upper (21%) extremities but may occur at any anatomic site , . Histologically, SS are divided into two major histological subtypes, monophasic and biphasic . In almost all cases (>90%), synovial sarcomas exhibit a characteristic translocation between Irsogladine X and 18. This translocation t(X;18) (p11.2;q11.2) involves the SS18 gene, located on chromosome 18 and one of highly homologous genes (SSX1 and SSX2) on the X chromosome . Approximately two-thirds of cases have a SS18/SSX1 fusion and one-third have a SS18/SSX2 fusion . Because expression of SS18–SSX1/2 has been observed in >90% of SS tumors, this is considered to play a central role in tumorigenesis . Curiously, biphasic SS commonly shows a SS18–SSX1 translocation, whereas monophasic SS may contain either the SSX1 or SSX2 translocation partner, without a clear predominance of either one .
The Ewing\'s sarcoma family tumor (ESFT) is the second most common bone malignancy after osteosarcoma . ESFT includes Ewing sarcoma of bone, extra-osseous Ewing sarcoma (ES), primitive neuroectodermal tumor (PNET) and Askin\'s tumors . ES is a disease affecting children and young adults with a peak incidence at age fifteen . The ES tumors arise in bones and soft tissues, primarily. However, ES may occur in other anatomic sites . Similar to several other sarcomas, ESFT exhibits an aggressive behavior with a tendency to recur and metastasize primarily to the lung, bone and bone marrow . Ewing\'s sarcoma is in more of 85% of the cases associated with the translocation t(11;22)(q24;q12), which leads to the formation of the EWS–FLI1 fusion gene which seems to have a oncogenic activity , . Several breakpoints were identified in EWS and FLI1 genes and heterogeneous fusion genes are formed. Three of these points are the most frequent; type 1 breakpoints accounting for 60% of EWS–FLI1 fusions occur in exon 7 of EWS gene and exon 6 of FLI1 gene; type 2 breakpoints occur in exon 7 of EWS gene and exon 5 of FLI1 gene; and type 3 breakpoints occur in exon 10 of the EWS gene and exon 6 of FLI1 gene .
The IGF2 gene and Hedgehog (HH) signaling pathway are fundamental during embryonic development, and are also implicated in the growth of a variety of tumors , . IGF2 gene is part of the insulin-like growth factor (IGF) signaling system, which plays a critical role in the growth and development of many tissues and regulates the overall growth, particularly in the prenatal period. Under normal physiological conditions, the IGF signaling is tightly controlled. The IGF system has been implicated in various pathophysiological conditions, and is thought to play an especially prominent role in tumorigenesis . The hedgehog signaling pathway is a critical component of embryonic development . While hedgehog signaling is generally absent and not essential in adult organisms, aberrant post-embryonic Hh signaling has been detected in a variety of pathological conditions including many pediatric and adult malignancies such as basal cell carcinoma (BCC), medulloblastoma and RMS .
The purpose of the present study was to investigate the prevalence of the PAX3–FOXO1 and PAX7–FOXO1 fusion genes in RMS samples, SS18–SSX1 and SS18–SSX2 in SS samples and EWS–FLI1 in ES samples by RT-PCR in Brazilian\'s sarcoma samples. Additionally, we investigated the IGF2, IHH, PTCH1 and GLI1 gene expression levels in these samples and try to relate them to the clinic-pathological parameters.
Material and methods
Discussion We performed RT-PCR to detect fusion genes in RMS, SS and ES samples. Additionally we performed the sequencing of RT-PCR products of a subgroup of transcript samples. We identified 18 SNPs, all of them described in SNP databases . However, we did not find any association between the SNPs investigated and any diseases, including pediatric sarcomas.