Pediatric Sarcomas
We are part of a collaborative effort at UCSF to study the biology of pediatric sarcomas and other pediatric cancers using genomic approaches.

Biology and Genomics of Pediatric Sarcomas 

Using both Whole Genome Sequencing (WGS) and RNA sequencing (RNAseq), our goal is to identify novel drivers of relapse and metastasis and to develop new tools that can help guide therapy for patients with high-risk disease. To date we have sequenced over 100 pediatric cancers using WGS and RNA sequencing. These massive datasets are available for analysis by trainees interested in computational analysis of cancer. In parallel, we also have an active effort to establish patient-derived xenografts from pediatric solid tumors, providing an unprecedented opportunity to develop genome-informed therapies and advance precision medicine. 

The two specific sarcomas we have focused most of our attention on are: 

Ewing's Sarcoma

Chromosomal translocations are frequent genetic events in the genesis of many human cancers. They are particularly frequent in tumors common in pediatric patients. In Ewing's sarcoma, the most common translocation is EWS/FLI-1.We are using a variety of approaches in both mouse and human primary cells to study the mechanism of EWS/FLI-1 mediated oncogenesis. We have developed a mouse model of Ewing’s sarcoma that closely recapitulates the EWS/FLI-1 translocation. In addition, we have used mesenchymal stem cells isolated from human patients in the pediatric age group to understand the consequences of EWS/FLI-1 translocation in the likely cell of origin. These studies have led us to identify an important role for long, non-coding RNAs in the biology of EWS/FLI-1.  Our laboratory was the first to describe a role for lncRNAs in this disease.  Our current efforts re directed at identifying the molecular function of Ewing Associated Transcript 1(EWSAT1) and other lncRNAs that are regulated by EWS/FLI-1.

Osteosarcoma 

Our laboratory is also interested in Osteosarcoma, another bone cancer that is most commonly seen in adolescents and young adults. In contrast to Ewing's sarcoma, where the initiating genetic event is well understood, the molecular cause of Osteosarcoma is not well defined. A key problem for advancing Osteosarcoma research is that this is a rare disease and primary tumor samples from patients are difficult to obtain.

Through a collaboration with several sarcoma centers (UCSF, University of Washington,  Stanford), we have established a large (over 20 to date) bank of primary xenograft samples from both pre and post-chemotherapy patient biopsies from Osteosarcoma patients. This is a rich resource for translational studies to understand the molecular underpinnings of Osteosarcoma development, chemoresistance and metastasis. Current efforts are directed at identifying mediators  of osteosarcoma metastasis and the role of copy number amplified genes as drivers of osteosarcoma progression.