Molecular e functional characterization of bone and soft tissue sarcomas of children and adolescents

Abstract

Sarcomas are a heterogeneous group of malignant tumors with a high frequency in children. From a genetic standpoint, sarcomas can be divided into two main groups, which are distinguishable by cytogenetic findings. One group is characterized by the presence of simple karyotypes, near diploid, with a few specific chromosomal changes, which include the rhabdomyosarcoma (RMS), Ewing's sarcoma (ES) and synovial sarcoma (SS). The second group presents complex karyotypes with a high degree of genomic instability, in which it characterizes osteosarcoma (OS). Although chemotherapeutic agents and surgical techniques vary with the type of cancer and location of disease, sarcomas, bone and soft tissue share a common characteristic: the survival curves for these diseases remain stagnant in the last two decades, despite the numerous clinical protocols and various agents used. The objective of this study will be the evaluation of the expression profile of fusion and development genes in RMS, SE and SS, and the role of MAPK7 gene in OS. RT-PCR, qPCR will be performed to analyze the fusion genes: PAX3-FKHR, PAX7-FKHR, EWS-FLI1, SYT-SSX1, SYT-SSX2 and development genes: IGF2, IHH, GLI1 and PTCH1 in RMS, SE and SS tumors. In OS evaluate if the increased expression of the MAPK7 gene, observed in a previous study, is results from a mutation of this gene by sequencing. It will be performed MAPK7 gene silencing and later we will carry out technical viability, proliferation, apoptosis, migration and invasion in silenced and not silenced OS cells, so that we can elucidate the role of MAPK7 gene as a possible prognostic marker in OS. (AU)