Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma.

Periacetabular resections for primary bone sarcoma and metastatic disease require reconstruction to restore weight-bearing along anatomic axes. We designed a modular hemipelvic prosthetic system to reconstruct the pelvis and evaluated the early clinical outcome of the prosthesis using 3-year survival rate, local recurrence rate, Musculoskeletal Tumor Society (MSTS) 93 function score, and complications. We retrospectively reviewed 28 patients who had pelvic tumor resections and reconstructions using the new hemipelvic prostheses between 2001 and 2005. Sixteen (57.1%) patients had Types II and III (periacetabular and pubis) pelvic resections, seven had Types I and II (periacetabular and ilium) pelvic resections, and five had Type II (periacetabular) pelvic resection. Six patients with osteosarcoma had chemotherapy. None received radiation therapy. Patient survival status, function, and complications were evaluated at a mean followup of 30 months (range, 10-59 months). Fifteen patients were free of disease, eight patients died of disease, and five patients were alive with disease. The overall survival rate was 67.1% at 3 years. Twenty-five percent had local recurrence and 21% had metastasis. The mean MSTS 93 score was 60. Deep infection occurred in four patients; dislocation occurred in one patient. The results are encouraging because of the acceptable complication rate and satisfactory functional outcome.