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Bone Sarcoma Biology: 20 years Later Biology Treatment (Prognostication) Sarcomas with specific reciprocal translocations Sarcomas with complex unbalanced karyotypes Biological Insights/Prognostic Factors • Important to identify and describe, even more critical will be to validate. • Three interesting candidates in osteosarcoma presented. • Identified using very different modalities – integrative analysis, deep sequencing, proteomics. Nalan Gokgoz 53 gene signature for outcome Tadashi Kondo Peroxiredoxin2 correlates with response to induction Leonardo A. Meza-Zepeda RNA and DNA sequencing identified a translocation between chromosome 17 and 6, involving the PMP22 and ELOVL5 genes respectively. Therapeutic Approaches Francois Lamoureux Ymera Pignochino Inhibition of clusterin with OGX-011 is synergistic with zoledronate in osteosarcoma Trabectidin and PARP-1 inhibition is synergisic Randomized phase 2 trial in chondrosarcoma – Andrew Wagner • Hedgehog pathway - strong preclinical rationale • Appropriate design and PFS endpoint – challenging disease • The planned biology studies may help understand the trial results further