Zebrafish Functional Genetics Approach to the Pathogenesis of Well-Differentiated Liposarcoma
Abstract
Well-differentiated liposarcoma is the most common human sarcoma, and exposure to herbicidal agents used during the Vietnam war is a key predisposing factor. However, the pathobiology of this disease is very poorly understood, and there are no effective therapies for patients with unresectable disease. Almost all tumors have amplifications of multiple genes located on chromosome 12q, but the lack of animal models previously made it impossible to define the key "driver" oncogenes within these amplicons. Our overarching hypothesis is that defining the oncogenes driving selection for 12q amplifications in well-differentiated liposarcoma will reveal highly productive molecular targets for therapeutic intervention. During Year 1 of this award, we performed all work proposed under Aim 1 of our original proposal to test the hypothesis that FRS2 (fibroblast growth factor receptor substrate 2) is a 12q oncogene that activates oncogenic signal transduction, using FRS2 overexpression in genetically engineered zebrafish models and in normal human preadipocytes. Work during the upcoming year will focus on Aim 2 of our original proposal, testing the hypothesis that MDM2, CDK4 and HMGA2 are key liposarcoma oncogenes, and on developing novel therapeutic strategies for patients with these tumors, which are highly resistant to conventional therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA619141
Entities
People
- Alejandro Gutierrez