Involvement of MET/TWIST/APC Combination or the Potential Role of Ossification Factors in Pediatric High-Grade Osteosarcoma Oncogenesis

Abstract

Dysregulated cell growth or differentiation due to misexpression of developmental critical factors seems to be a decisive event in oncogenesis. As osteosarcomas are histologically defined by malignant osteoblasts producing an osteoid component, we prospected in pediatric osteosarcomas treated with OS94 protocol the genomic status of several genes implied in ossification processes. In 91 osteosarcoma cases, we focused on the analysis of the fibroblast growth factor receptors (FGFRs) TWIST, APC, MET by allelotyping, real-time quantitative polymerase chain reaction, gene sequencing, protein polymorphism study. Our study supports the frequent role of TWIST, APC, MET as osteosarcoma markers (50%, 62%, 50%, respectively). TWIST, MET were mainly found to be deleted, no additional APC mutation was identified. Surprisingly, FGFRs are abnormal in only < 30%. Most of these factors, their abnormalities seem to be linked more or less to one clinical subgroup, but the most significant correlation is the link of MET, TWIST, APC abnormalities to a worse outcome, their combination within abnormal tumors. A wider cohort is mandatory to define more robust molecular conclusions, but these results are to be considered as the beginning of a more accurate basis for diagnosis, in search of targeted therapies, to further characterize prognostic markers.

Keywords

• Pediatric osteosarcoma
• osteogenesis
• TWIST
• APC
• MET