Background Identification of new genes that are mutated in osteosarcomas is critical to developing a better understanding of the molecular pathogenesis of this disease and discovering new targets for therapeutic development. Methods We identified somatic non-synonymous coding mutations in oncogenes associated with human cancers and hotspot mutations from tumor suppressor genes that were either well-described in literature or seen multiple times in human cancer sequencing efforts. We then systematically characterized 961 mutations in 89 genes across 98 osteosarcoma tumor samples and cell lines. All identified mutations were replicated on an independent platform using homogeneous mass extend MALDI-TOF (Sequenom hME Genotyping). Results We identified 14 mutations in at least one osteosarcoma tumor sample or cell line. Some of the genetic changes identified were in tumor suppressor genes previously known to be altered in osteosarcoma: p53 (R273H, R273C, and Y163C) and RB1 (E137*). Notably, we identified multiple mutations in PIK3CA (H1047R, E545K, and H701P) which have never previously been observed in osteosarcoma. Additionally, we observed mutations in KRAS (G12S), CUBN (I3189V, seen in two separate tumor samples), CDH1 (A617T, seen in two separate tumor samples), CTNNB1 (N287S), and FSCB (S775L). Conclusion We performed the largest mutational profiling of osteosarcoma to date and identified for the first time several mutations involving the PI3 kinase pathway – adding osteosarcoma on to the growing list of malignancies with PI3 kinase mutations. Additionally, we initiated a mutational map detailing DNA sequence changes across a variety of osteosarcoma subtypes and offered new candidates for therapeutic targeting.

Sunitinib is a tyrosine kinase/angiogenesis inhibitor with proven efficacy in gastrointestinal stromal tumor and advanced renal cell carcinoma. We are presenting the case report of a patient with aggressive alveolar soft part sarcoma with lung and bone metastases, who had failed multiple chemotherapy regimens showing significant response to sunitinib. There was not only complete regression of the primary tumor, stabilization of his bone metastases and significant improvement in the quality of life. Our report shows that sunitinib has the capability of playing a pivotal role in the management of non-gastrointestinal stromal tumors like alveolar soft part sarcoma. Further research and trials must be encouraged over the use of this drug as it is most definitely promising.

Management of soft tissue sarcomas can be very challenging because they have a high rate of metastasis, especially to the lungs, and respond very poorly to the currently available chemotherapeutic drugs. We present a case of epithelioid sarcoma in which complete remission of pulmonary metastases was observed after treatment with a single agent, navelbine, a vinca alkaloid, and a potential therapeutic agent. The patient has been persistently free of metastases for 4 years since treatment with navelbine. Further studies are warranted to establish the role of navelbine for the treatment of soft tissue sarcoma and their metastases.

Bortezomib with or without dexamethasone has been reported to be very effective and well tolerated in the treatment of AL amyloidosis. Commonly reported adverse effects are fatigue, nausea, vomiting, diarrhea, constipation, postural hypotension from autonomic neuropathy, peripheral neuropathy, thrombocytopenia and anemia. Dyspnea has been rarely reported as an adverse effect of bortezomib therapy in AL amyloidosis. We are reporting three case reports of patients suffering from AL amyloidodis, who had new onset acute dyspnea secondary to bortezomib treatment that required drug discontinuation. There might be some correlation between the AL amyloidosis disease and bortezomib associated dyspnea, but the pathophysiology is poorly understood.

All-trans-retinoic acid represents a major progress that has made acute promyelocytic leukemia the most curable subtype of acute myeloid leukemia in adults. Although all-trans-retinoic acid is usually well tolerated, some patients develop the retinoic acid syndrome, characterized by unexplained fever, weight gain, respiratory distress, interstitial pulmonary infiltrates, pleural and pericardial effusions, episodic hypotension, and acute renal failure. Further studies of growth factor expression and modulation of adhesion molecules are warranted to provide further insights into the pathogenesis of the syndrome and may lead to its prevention.